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?

Dr Mike's upper-class mother visits from Boston, disapproving of her daughter's choices, acquainting herself with her daughter's new family. Robert E suffers burns. Dr Mike is evicted from her makeshift clinic by the bank.

When a starving orphaned immigrant takes desperate measures to feed his siblings, the only thing standing between him and a noose is Kid Cole, the new sheriff.

Loren, the unforgiving father-in-law, threatens to take back Sully's homestead.

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

When the town's water supply is tainted with mercury by a wealthy mining baron, many people become sick and Dr. Mike threatens the miner to clean it up or have his land taken away.

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.

While out on a walk with Sully, Brian climbs a tree to show he could fly like the eagle in Sully's story but falls and hits his head. At first every thing seems fine and the town gets ready to build a school house. Brian is really excited about it and goes to help Loren but loses his sight. Loren rushes him to Dr. Mike. Although she is certain of what it is she does not know how to fix it. She wires for a doctor in Boston to advise as to nearest specialist. Dr. Mike refuses to leave his bed side and when they finally get word that the specialist is coming they find that he had slipped into a coma. Sully finally shows back up after being gone for two days and Michaela being so scared blames Sully. When they find that the stage coach will take longer to get here Dr. Mike realizes that there is no other way but to do the operation herself.

A woman dies and they find a hidden boy at her house. Dr. Mike takes the boy in while they try to determine who he is and if he has any family.

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. Mike and the reverend are skeptical when a so-called religious healer comes to town.

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

Dorothy thinks she's pregnant, but Dr. Mike's exam reveals there are other problems going on. The upcoming Sweetheart Dance causes trouble between Sully and Dr. Mike. Colleen and Becky squabble over a boy, while Dr. Mike suspects something fishy going on between Sully and Dorothy.

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.

Dr. Mike has an "A Christmas Carol" style dream, where she wonders what her life would have been like if she had not become a doctor.

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.

When a former circus performer and her daughter bring their circus to Colorado Springs, most of the town is recruited as performers.

When Rev. Johnson sponsors an orphan train in Colorado Springs, he finds placing the children in suitable homes may be harder then he anticipated.

Matthew gets hooked on gambling. Rev. Johnson's past catches up to him.

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

Doctor Michaela is abducted by Native Americans.

The town decides they need a town mayor. Jake Slicker and Dr. Mike are nominated to run against each other.

After Myra quits working for Hank, he drinks himself into a coma and Myra is the only one willing to stay by his side.

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.

Elizabeth sends crates of books from Michaela's deceased father's collection, prompting her to open a public library. Many become alarmed at the content of some of the books and want to prevent people from reading them.

Brian rescues a man from a trap who has horrific burns to his face from a train crash. Michaela decides to perform reconstructive surgery to repair his face.

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.

Sam Lindsay, an older independent woman, decides to end her medical treatment and take off into the wilderness. Dr. Quinn accompanies her and learns from the journey. Myra Bing goes into labor and Colleen finds what she is capable of.

Colleen and Brian's biological father Ethan returns to town with a new wife, intending to take the children away from Dr. Quinn. The children don't want to go but a court hearing seems to work against Sully and Dr. Mike, who they consider their parents.

Colleen and Brian run away to keep their father from taking them away from Dr. Mike and Sully. After they are found it's discovered Colleen has developed pneumonia. Dr. Mike realizes she has to let them go to save them.

The town puts on a production of "Romeo and Juliet". Brian tries to learn what love is so he can write a paper for school.

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 Dr. Mike becomes increasingly absorbed in her romantic life with Sully, Colleen, feeling rebellious, joins her school friends in dangerous and questionable escapades. When Brian also begins to feel ignored, Mike and Sully realize how important it is to balance their new life.

Brian's dog Pup gets bitten by a rabid raccoon. Then Matthew's fiancée gives the dog water. She also gets bitten.

Elderly Abner Foley comes to town looking for alternative treatment and a very friendly dog adopts Jake Slicker. The rest of the town looks forward to the costume party but first Brian must face a very big fear.

Dorothy gets her book about the town published, but the townsfolk read her depiction of them differently than she intended.

Dr. Mike intends to climb up Pike's Peak as part of a birthday celebration to the derision of the men. Grace, Dorothy, and Myra decide to join her. Jake and Preston plan a casino with the doctor away.

Dr. Mike injures herself after the other women have turned back on their quest to climb Pike's Peak. Sully steps in for his wife on the council to thwart Jake and Preston's casino plans. Grace, Myra, and Dorothy change their minds and head back up the mountain.

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.

Dr. Mike and her family receive an unexpected gift from Boston, a small poodle unsuited to life on the frontier. Brian has his first crush on Sara, Preston is embarrassed by a painful kidney stone, and the Reverend plans a living nativity.

As the town grows, a rowdier element is evident and the citizenry wants a little more law and order. Matthew believes he is suited for the job of sheriff but refuses to carry a gun which worries Dr. Mike.

After a long period of grieving over his lost fiancée, Matthew finally finds love again, but the object of his affection works at Hank's saloon.

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

News from his former mentor's upcoming visit has the Reverend Johnson rushing to ensure he makes a good impression. He quickly attempts to raise enough money to fix up his dilapidated church.

When a stranger is convicted of raping a young girl and murdering an old man, he is sentenced to death. Some people are conflicted about whether or not it is right to take "an eye for an eye".

Dr. Mike is nominated for Colorado's Woman of the Year and the town regales the judge with her accomplishments. Hank's Nana comes to visit and he "borrows" Myra and Samantha to pose as his family.

Isabelle Maynard, an attractive painter, arrives in town attracting the eligible bachelors particularly Preston. But after the citizens learn Isabelle has leprosy they are determined to drive her out of town over Dr. Mike's objections.

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.

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.

When he gets the papers for his divorce from Myra, Horace attempts suicide and almost succeeds. His friends do what they can to help him, but it turns out that depression isn't always cured that easily.

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.

After Myra quits working for Hank, he drinks himself into a coma and Myra is the only one willing to stay by his side.

When Rev. Johnson sponsors an orphan train in Colorado Springs, he finds placing the children in suitable homes may be harder then he anticipated.

The town decides they need a town mayor. Jake Slicker and Dr. Mike are nominated to run against each other.

When he gets the papers for his divorce from Myra, Horace attempts suicide and almost succeeds. His friends do what they can to help him, but it turns out that depression isn't always cured that easily.

Dr. Mike injures herself after the other women have turned back on their quest to climb Pike's Peak. Sully steps in for his wife on the council to thwart Jake and Preston's casino plans. Grace, Myra, and Dorothy change their minds and head back up the mountain.

After a long period of grieving over his lost fiancée, Matthew finally finds love again, but the object of his affection works at Hank's saloon.

Sam Lindsay, an older independent woman, decides to end her medical treatment and take off into the wilderness. Dr. Quinn accompanies her and learns from the journey. Myra Bing goes into labor and Colleen finds what she is capable of.

Dr. Mike intends to climb up Pike's Peak as part of a birthday celebration to the derision of the men. Grace, Dorothy, and Myra decide to join her. Jake and Preston plan a casino with the doctor away.

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.

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.