When Zoe reads about her fellow classmates' accomplishments in her Alumni magazine, she is upset that they list her as "retired" and invites the reporter to BlueBell for an interview. However, Zoe has a hard time convincing the reporter that she actually has a thriving medical practice in BlueBell - that is, until she comes across a rare and potentially serious disease. Trying to be considerate of Lemon's feelings, George informs her that he is going out on a date, making her feel that she too needs to find a date. Meanwhile, Lemon and Lavon both find themselves in competition with their nemesis Ruby.
Fast-talking New Yorker and brand new doctor Zoe Hart has it all figured out - after graduating top of her class from medical school, she'll follow in her father's footsteps and become a cardio-thoracic surgeon. But when her dreams fall apart, Zoe decides to accept an offer from a stranger, Dr. Harley Wilkes, to work with him at his small practice in Bluebell, Alabama. Zoe arrives in this small Gulf Coast town only to find that Harley has passed away and left his half of the medical practice to her in his will.
She quickly finds that Southern hospitality isn't always so hospitable - the other doctor in town, Brick Breeland, is less than pleased to be sharing the practice with this young outsider, and his daughter, Lemon, is a Southern belle whose sweet disposition turns sour when she meets Zoe. Zoe's only allies are the mayor, former football star Lavon Hayes, her bad-boy neighbor Wade Kinsella, and handsome lawyer George Tucker - who just happens to be Lemon's fiance. Zoe is out of her element and ready to pack her bags, but a surprise visit by her snobby New York mother leads to Zoe's decision to stay in Bluebell for a while, discovering small-town life and a side of herself she hadn't known was there.