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?

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

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

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.