Michaela Quinn, a female doctor in post-Civil War Boston, Massachusetts, finds more than she bargained for when she answers an ad for a doctor in a small town in the Colorado territory.

Miss Olive arrives back in town and believes that she should be the one looking after Matthew, Colleen and Brian. She brings with her a sick cowboy who had contracted influenza but everyone is unaware of the exact nature of his illness. Michaela attempts to try her hand at cooking but is unsuccessful. After the cowboy dies and his child becomes ill with the same thing Dr. Mike discovers that it is influenza. People in the town were dying and Dr. Mike wanted to quarantine people who are sick in Charlotte's boarding house. Brian comes down with the influenza and Colleen begins to think that Dr. Mike only wants to treat people instead of being their guardian and starts to resent her. Dr. Mike is running out of medicine and Sully suggested Cheyenne brewed tea but she does not want to administer a drug she is not familiar with. Dr. Mike uses the last bit of medicine for Jake, Brian and Horace. Brian's fever finally breaks and Dr. Mike is relieved but she herself now has influenza. Sully had Matthew go for Cloud Dancing, Medicine Man. Will they get back in time?

Michaela worries when Charlotte's husband, Ethan Cooper, comes back to the family he abandoned, convincing almost everyone of his newfound ways.

When Doc Eli, a medicine-show man, arrives in town professing to have created the perfect bottled elixir, Mike sets out to call his bluff, especially when her children's health becomes jeopardized.

A wandering cowboy abandons his baby boy and leaves him in Dr. Mike's care.

The railroad hires men to kill off all the buffalo, which the Cheyenne need to survive, and Sully gets hurt when he tries to stop the men.

When Cheyenne medicine man Cloud Dancing is wounded by General Custer, who intends to hang him, Sully and Dr. Mike join forces to help him escape.

As Dr. Mike's birthday approaches, the kids decide to do something about her unmarried status

Matthew and Michaela are at odds over his future when he sets out to prove to others -- and to himself -- that he's a grown man ready to take on life -- and decides to marry Ingrid.

Colleen believes that she loves Sully and that he returns her feelings when he saves her from a runaway wagon. She and her friends had been reading romance stories in a weekly publication and in one of them the woman is captured but writes a letter to her love, and he saves her. She decides to write a letter to Sully and goes into the mountains in hopes that he will find her. Lewis finally gets the letter to Sully by giving it to Dr. Mike who reads it first and informs Sully of what was going on. Hank accuses Grace of trying to poison him with her cooking.

A famous civil war photographer realizes he may be taking his last picture after Dr. Mike discovers that he is going blind.

Snowbird gives Dr. Mike a horse she wants to enter in the Territory Stakes horse race, but she must disguise herself as a man to qualify. Sully teaches her what to do to fool the race officials and helps her with strategies for the race.

Loren's sister-in-law Dorothy comes to town to flee her abusive husband. He ends up dead, and she is tried for his murder.

Mike is forced to rethink her relationship with Sully after a visit from his ex wife's ghost.

While hunting, Jake accidentally kills the Cheyenne brave Little Eagle and Sully tries to keep the peace between the Cheyenne and the town.

Dr. Quinn's mother in Boston is ill. Dr. Quinn takes the children to Boston.

There is a drought and no food for the town's Thanksgiving dinner. The townspeople fight over water.

Dr. Quinn is called away to a Flu epidemic in another town. Leaving Sully in charge of the children. But when there is an explosion at the railway, the military puts a bounty out for Sully. Sully is shot, leaving Colleen to treat him.

The army brings supplies to the Cheyenne as an offering for their land. Dr. Quinn advises them to take the supplies in order to ease their suffering through the harsh winters. However, the supplies harbor a hidden surprise for the Cheyenne.

A troop of buffalo soldiers comes to town and with them the idea that the government was using them instead of white soldiers, because it was felt they were more expendable.

Dorothy's son returns from war with a problem that many vets came home with.

Doctor Michaela is abducted by Native Americans.

With the help of Cloud Dancing and his son, Sully is determined to rescue Dr. Mike.

A stranger with close ties to Dr. Quinn comes to town with an agenda of his own.

Dr. Mike has a decision to make.

Dr. Mike and the citizens of Colorado Springs look forward to the advantages a train could bring to their small town, but Sully and the Cheyenne fear progress could lead to their demise. While Loren and Jake are creating a false campaign of the town's highlights to lure the railroad developers to the area, Mike and Sully disagree about whether or not they should build their future and their new home in a town undergoing such change. While the engaged couple searches for a compromise, Colleen befriends a Chinese railroad laborer, named Peter, who has encountered hostile discrimination during his stay.

When Loren sets out to prove he's not too old, and Brian wants to prove he's old enough, the two embark on individual journeys that intersect. Loren shocks everyone when he announces that he's going to travel to Bolivia, to prove to himself and to everyone else that he's not too old for the treacherous adventure. While he's away, Brian takes off on his own little adventure -- to camp out alone at night and brave the elements. But an unexpected travel companion -- a grizzly bear -- unites the two "men" in a shared adventure neither anticipated.

Cloud Dancing and the rest of the Cheyenne are told to move to a reservation where they would be dependent on handouts. Dr. Mike, Sully, and the children head to Washington to lodge a complaint and get the order changed.

Arriving in Washington, Dr. Mike and Sully find it difficult to find anyone to listen to their concerns. Sully is arrested for army desertion while a plot against the president is overheard. Michaela must break Sully out of jail to expose the conspiracy.

When money becomes short for Sully, he tries everything to make ends meet rather than accept help from Dr. Mike.

Dr. Mike and Sully are traveling through obnoxious Native American territory when their stagecoach is robbed and they are abandoned. With them are a just married Kid Cole and Sister Ruth as they try and reach home for Thanksgiving. Evading hostile tribesmen is only the beginning.

The town's Christmas spirit is in question when a family who are Jewish immigrants moves to town.

Sully is appointed Indian agent to the Cheyenne and approaches it in an idealistic fashion. When the food intended for the tribe is diverted and illegal alcohol is plentiful, Sully becomes angry. He vows to discover the truth with the help of Dr. Quinn and her family.

A newspaper report of a comet's imminent collision with Earth causes hysteria in town over the end of the world.

Ah abrasive Dr. John Porter arrives in town after hearing of the discovery of dinosaur bones. After learning they were found in a sacred Indian burial ground, he proceeds to spoil grave sites under the protection of the US Army. Cloud Dancing and the Cheyenne retaliate by taking the remains of the white settlers.

Dr. Mike and Sully convince Chief Black Kettle that he should move his starving people to a new reservation. Dr. Mike and Sully are both working on wedding presents for each other.

When Dr. Mike and Sully hear there is trouble for the Cheyenne at their new home, they travel there with Cloud Dancing only to find the whole tribe was massacred. Dr. Mike is devastated after the massacre because she felt she should have stopped it.

Dr. Mike and Sully go to Rev Johnson for a honest discussion regarding their upcoming marriage.After originally agreeing they have no conflicts, the couple begin reliving their past difficulties via prior show clips since they first met.

The town of Colorado Springs is preparing for an event of a lifetime, the marriage of Sully and Dr. Mike. Unexpected guests include Dr. Mike's mother Elizabeth Quinn and two of her sisters Rebecca and Marjorie. They have brought with them enough Boston finery to pull off a splendid society wedding. Meanwhile General Custer has put out a bounty on Cloud Dancing which could interfere with the wedding.

Bolstered by the long-awaited arrival of the railroad, the citizens of Colorado Springs busily prepare for the biggest social event in the town's history, the wedding of Dr. Mike and Sully. The first train carries some surprise visitors, Dr. Mike's mother, Elizabeth, and sisters Marjorie and Rebecca, who have unexpectedly traveled all the way from Boston for the occasion. However, their elaborate wedding plans threaten to ride roughshod over the townsfolk's more homespun arrangements. Sully, meanwhile, is crestfallen to learn that Gen. Custer has placed a bounty on the head of his close friend Cloud Dancing, who he had planned to have as his Best Man.

Dr. Mike and Sully return from their honeymoon and begin unpacking at their new homestead. A Boston banker comes to town and stirs up controversy among the townspeople as the inevitability of progress ensues.

Loren convinces the town to pay a baseball team to visit for an exhibition game against the town's team. The two teams will share the ticket sales, but problems arise when it's discovered Loren didn't read the fine print.

As the community prepares to celebrate Thanksgiving, Dr. Mike and Sully become anxious with their inability to conceive. As the couple try to get used to the idea of not having a baby, Jake becomes depressed about being alone.

When a charlatan passes through town selling shares in a nonexistent invention, nearly everyone in Colorado Springs buys into the scam.

When Ezra Leonard offers a $1000 reward to the capture-dead or alive- of the mountain man who kidnapped his son, Sully's rescue party turns into an unruly mob. Dr. Mike must accept help from Dr. Cassidy to save her pregnancy.

Even though Dr. Mike and the Reverend Johnson favor the opening of a Indian school on the reservation, Cloud Dancing sees it as the final destruction of Indian culture.

Dr. Mike's dearest friend from college comes to visit her in Colorado Springs, both women are initially happy to see one another, but soon resort to their competitive relationship of years past.

Dr. Mike, nearing her pregnancy's end, has her plans for scaling back interrupted when Cloud Dancing is stabbed and Emma needs an operation. Matthew wants Emma to leave Hank's employment when she's better.

A young brave kills a soldier in self defense, but Cloud Dancing confesses to it to protect him. Dr. Mike and Sully defend Cloud Dancing during his trial for murder.

Dr. Mike's mother and two of her sisters arrive with a young Dr. Cook to deliver the baby. Conflict arises between Horace and Myra which ruins Preston's hotel groundbreaking. Sully works to prevent Cloud Dancing's transfer to another reservation.

Dr. Mike leaves in the night to treat Sully, who was wounded by sergeant O'Connor while helping Cloud Dancing. She goes into labor with only Sully to assist her.

Finally ready to work again after giving birth to her baby, Dr. Mike must lead a rescue party when Sully and Cloud Dancing are among the passengers on a train that has been overtaken by robbers and wrecked. Sully had negotiated Cloud Dancing's release from Army detention, and the two were taking the train to Colorado Springs when a gang of thieves derailed the train in an effort to rob it. Meanwhile, Dr. Mike must again face the prejudice against women doctors when she finds that the townspeople have become used to being treated by young Dr. Andrew Cook who filled in for her while she was on maternity leave. For his part, Andrew has become reluctant to return the practice to Dr. Mike and go back to Boston, as originally agreed.

Dr. Mike is charged with malpractice and must stop treating patients during the lawsuit, leaving medical matters to the young and reluctant Dr. Cook.

Colleen considers leaving college when the famous singer, Gilda St. Clair, offers her a job traveling the world with her.

When Sully is offered a job helping to survey the new National Park at Yellowstone in Wyoming, Dr. Mike is faced with the prospect of leaving her practice and all their friends and moving into the wilderness. With Sully no longer acting as the local Indian agent and banned from the Indian reservation, Dr. Mike realizes that it is important for him to have work that is meaningful to him. Leaving everything and everyone she knows and taking their new baby into the wilderness, however, is a daunting prospect for her. Meanwhile, as Matthew and Emma think about marriage, Brian agonizes about his first date at the Sweethearts' Dance, and Dorothy teaches Cloud Dancing some ball room dances while he provides her with background on Indian customs for a book she is writing.

When Jake and Preston run against one another for mayor of Colorado Springs, they both want Dr. Mike's endorsement, until she is arrested and thrown in jail for treating a fugitive Indian. After Sully and Cloud Dancing rescue the Indian from the Army and Dr. Mike is arrested for treating his wounds, Dorothy hatches a plan to set her free. Meanwhile, with the election only a few days off, Jake promises Robert E a seat on the City Council if he can deliver the black vote, and Jake and Preston hold a debate so that the townspeople can decide who is the better man.

Dr. Mike, Sully and Brian are drawn into the middle of Colorado Springs' racial problems when Grace and Robert E try to enroll their son, Anthony, in the all white school. After Jake is forced to keep his campaign promise and make Robert E a member of the town council, Robert E sets up a school for the black children in shanty town. Since no white teacher will teach the children, however, the job falls to Grace. When it becomes apparent that Anthony needs much more advanced schooling than the black school can provide, Grace, Robert E and Brian try to get him into the white school. Meanwhile, Jake and Hank open their own hotel to rival Preston's new one, and the battle for business escalates.

Dr. Mike desperately attempts to find out why patients are dying mysteriously after having been treated in her clinic. As Dr. Mike searches for the answer to why a deadly and mysterious infection haunts her clinic, the townspeople begin to fear coming in for treatment. Unable to find out what is causing the deaths, Dr. Mike then makes a fateful decision that could mean destroying everything she has worked for through the years. Meanwhile, the attraction between Colleen and Andrew grows while she is home from college for a visit.

Brian suffers a crisis of faith when the Rev. Johnson is suddenly stricken with progressive blindness at Christmas time and Dr. Mike can't help him. The townspeople are saddened by the Rev. Johnson's affliction, but Brian sees the malady as God's way of punishing the clergyman. The Reverend Johnson's faith is also tested and he decides not to lead the Christmas Eve service. Meanwhile, Dr. Mike consults with Cloud Dancing about the situation, and it's he who finds the words for Dr. Mike to explain to Brian and the Rev. Johnson that they should not consider the blindness a punishment from God, but instead a message that the preacher is to take a new path

Dr. Mike sees that the marriage of Kid Cole and Sister Ruth is unraveling and the couple is heading for divorce for no apparent reason. Johnny Cash and June Carter Cash reprise their roles as Kid Cole and Sister Ruth. When Cole and his wife stop to see Dr. Mike while escorting mail-order brides to San Francisco, Dr. Mike immediately feels the tension in the air between them. She then learns that Cole is terminally ill and, in an attempt to spare Ruth the agony of watching him die, has created problems in their relationship so Ruth won't feel obligated to care for him. Ruth, meanwhile, is devastated at her husband's behavior and talk of divorce and seeks Dr. Mike's advice.

When Colleen, who is working on a college paper, asks Dr. Mike to recall her most memorable case, Dr. Mike looks back on the five turbulent years she's lived and loved in Colorado Springs. As they sit with Andrew, who is mysteriously ill at the clinic, Dr. Mike reminisces about her tumultuous career -- its successes and its failures -- and realizes how many divergent cases she has seen and treated. When Andrew's condition takes a turn for the worse, Dr. Mike warns Colleen about the fine line between emotional involvement and professional detachment, an issue with which she has long struggled in the frontier town that's now her home.

Sully's best friend Daniel arrives for a visit, but the relationship becomes strained when Daniel offers Sully money at a time when Sully desperately needs it to save the homestead.

After Preston calls the loan due on the homestead while Sully is gone, Dr. Mike reluctantly accepts Daniel's offer to pay it off, further straining relationships. Things are also complicated because Daniel has fallen in love with Dr. Mike.

Dr. Mike, Brian and Katie are taken hostage at the homestead by bank robbers, one of whom is wounded. After Dr. Mike is taken hostage by Brent and Huston, she watches helplessly as Sully, returning from a trip is shot by Brent as he approaches the house. In spite of his injury, Sully, with the help of Wolf, Cloud Dancing, Matthew, Hank and Andrew, plots a rescue plan. Meanwhile, inside the house with the two desperate robbers, Dr. Mike and Brian do some quick thinking and - with the help of some chloroform - distract the men while they scramble to come up with an escape scheme of their own.

After Cloud Dancing is beaten almost to death, Sully organizes an escape for him and the others on the reservation, which turns deadly. Sully flees with a price on his head.

Sully tries to get Cloud Dancing to safety in the north. The actions of the renegade dog soldiers take their toll on the town. An old enemy goes after Sully and Cloud Dancing.

After Sgt. O'Connor is found dead at the bottom of a cliff, everyone fears that Sully died too in the fall. Dr. Mike and friends go looking for Sully. Matthew quits as sheriff. The Dog Soldiers continue raids on the town.

Dr. Mike, Matthew, Brian and Daniel find a seriously wounded Sully and move him to a cave near the homestead so they can nurse him back to health while hiding him. Dr. Mike starts working to clear Sully's name.

General Wooden is injured by dog soldiers and dies. Daniel talks with Sgt. McKay and the non-violent Indians are let free. Hank takes over as sheriff temporarily. Daniel runs for sheriff and wins. Sully and Cloud Dancing work for peace.

Dr. Mike worries about how to tell Robert E. and Grace that their adopted son Anthony may not survive his mysterious illness. Meanwhile Sully struggles with convincing the renegade braves to return to the reservation and learning about Dr. Mike's recent miscarriage.

Marjorie, Dr. Mike's sister returns to town as a member of the Women's Temperance League to try to outlaw alcohol. Jake starts believing that there may be something going on between Hank & Ms. Teresa. Meanwhile Grace has turned to drinking to help comfort the recent death of her adoptive son Anthony.

Dr. Mike matches wits with a notorious Indian hater, Maj. Samuel Morrison, as she tries to mediate a peace treaty between Black Moon's braves and the cavalry, which would include a pardon for Sully and allow him to return home. Dying of consumption, Black Cloud agrees to surrender if his braves are allowed safe passage to the reservation. Wellend Smith, an emissary sent by President Grant, sides with the Indians, but Maj. Morrison is determined to thwart the agreement and put them in prison. Mike and Sully must look toward Sgt. McKay for support in upholding the law

After accompanying Black Moon's braves safely to the reservation, Dr. Mike and Sully begin the trip home for Christmas but are delayed when they stop to help a hapless young married couple they find wandering in the wilderness. The young couple, Chester and Hallie, are former city dwellers trying to find a new settlement established by their relatives, but are hopelessly lost. Meanwhile, Daniel, who has been wandering all his life, is tempted to give up his job as sheriff to accept an offer to run a mining operation far away from Colorado Springs.

Dr. Mike is shot by a distraught man. On returning to work, she begins to become afraid that something bad will happen again and show signs of PTSD.

As Jake and Teresa look forward to their wedding day, Dr. Mike and Sully struggle to free Cloud Dancing, who was captured and put in prison for leaving the reservation. Dorothy is so disturbed at the thought of Cloud Dancing in jail that she contemplates helping him escape and fleeing with him into the wilderness. Meanwhile, Teresa introduces Jake to her visiting aunt, Dona Verano, and her cousin, Carlos, a priest. The visit turns sour when the older woman takes an immediate dislike to Jake and tries to prevent the marriage.

Michaela and Sully reminisce about the ups and downs of their relationship and make a momentous decision about their future. While returning from a week long trip with Sully, Michaela stumbles and falls, sustaining a head injury. The couple takes refuge in an abandoned cabin where Sully must keep Michaela awake to prevent her from slipping into a coma. Together, they reminisce about the myriad different experiences -- good and bad -- they've shared together and then make a pivotal decision about their future.

Dr. Mike's elation at Colleen's acceptance to medical school quickly turns to disappointment when Colleen chooses to marry Andrew before starting school. A bitter family argument erupts when Dr. Mike tells Colleen that she is less than overjoyed at her announcement and feels that the couple is rushing into marriage and should wait until Colleen completes medical school. Meanwhile, Jake's sale of his half of the Golden Nugget to Preston angers Hank; Robert E and Grace have wonderful news to share; the stock market crash hits Preston and the townsfolk hard, and Dorothy and Cloud Dancing reach a new level in their relationship.

When Dr. Mike and Sully hear there is trouble for the Cheyenne at their new home, they travel there with Cloud Dancing only to find the whole tribe was massacred. Dr. Mike is devastated after the massacre because she felt she should have stopped it.

A young brave kills a soldier in self defense, but Cloud Dancing confesses to it to protect him. Dr. Mike and Sully defend Cloud Dancing during his trial for murder.

Dr. Mike and Sully return from their honeymoon and begin unpacking at their new homestead. A Boston banker comes to town and stirs up controversy among the townspeople as the inevitability of progress ensues.

Even though Dr. Mike and the Reverend Johnson favor the opening of a Indian school on the reservation, Cloud Dancing sees it as the final destruction of Indian culture.

After Sgt. O'Connor is found dead at the bottom of a cliff, everyone fears that Sully died too in the fall. Dr. Mike and friends go looking for Sully. Matthew quits as sheriff. The Dog Soldiers continue raids on the town.

When Cheyenne medicine man Cloud Dancing is wounded by General Custer, who intends to hang him, Sully and Dr. Mike join forces to help him escape.

As Jake and Teresa look forward to their wedding day, Dr. Mike and Sully struggle to free Cloud Dancing, who was captured and put in prison for leaving the reservation. Dorothy is so disturbed at the thought of Cloud Dancing in jail that she contemplates helping him escape and fleeing with him into the wilderness. Meanwhile, Teresa introduces Jake to her visiting aunt, Dona Verano, and her cousin, Carlos, a priest. The visit turns sour when the older woman takes an immediate dislike to Jake and tries to prevent the marriage.

Sully tries to get Cloud Dancing to safety in the north. The actions of the renegade dog soldiers take their toll on the town. An old enemy goes after Sully and Cloud Dancing.

As the community prepares to celebrate Thanksgiving, Dr. Mike and Sully become anxious with their inability to conceive. As the couple try to get used to the idea of not having a baby, Jake becomes depressed about being alone.

There is a drought and no food for the town's Thanksgiving dinner. The townspeople fight over water.