Andy's neighbor and friend Nina (Stephanie Niznik) is ostracized by the townspeople when they discover she is a surrogate mother for a woman in her mid-50s. Andy's clumsy attempt to come to Nina's defense backfires, but she turns to him and Ephram for help when the baby makes an unexpectedly early arrival. Meanwhile, Ephram is dealt an emotional blow when Amy disinvites him to a party in order to gain the approval of her friends; and Delia attempts to befriend the school bully, Magilla (guest star Bret Loehr).

Dr. Brown and Dr. Abbott must put their striking differences aside to educate the town of Everwood after several of their teenaged patients are diagnosed with a sexually transmitted disease. To make sensitive matters worse, Dr. Abbott has reason to suspect that his son, Bright, may have been intimate with one of the patients. Meanwhile, Ephram pushes his romantic feelings aside to comfort Amy who is distraught over not being able to go to the Fall Dance with her boyfriend who remains in a coma.

Although conflicted by his feelings for Amy, Ephram finds himself serving as confidante and friend to Amy's boyfriend, Colin, who continues to feel like a fish-out-of-water as he attempts to reclaim his life before the accident. Meanwhile, Andy hopes to convince Ephram to resume the piano lessons he abandoned after his mother's death; Nina's absentee husband (guest star Dylan Walsh) comes home for a visit, which proves to be far from happily ever after; and in a bittersweet turn of events, Amy and Colin are nominated for Homecoming King and Queen.

On a church ski trip chaperoned by perpetual party pooper Dr. Abbott, Amy and Colin share their first kiss since the surgery. Ephram finds himself intrigued by Colin's younger sister, Laynie (guest star Nora Zehetner), who has recently returned home from boarding school. Also, Bright attempts to get to the next base with his girlfriend (guest star Devon Reilly). Meanwhile, Andy hesitantly agrees to attend a singles mixer with the recently divorced Reverend Keyes (guest star Tim Dekay).

Dr. Brown faces one of the toughest moral decisions of his career when a distraught pregnant teenager (guest star Kate Mara) and her father (guest star Kevin Tighe) come to him for guidance about terminating her pregnancy. Meanwhile, Ephram is humiliated in front of the entire school when his date for the Spring Formal ditches him at the dance to make-out with her boyfriend. Lastly, Amy and Colin (Mike Erwin) have a huge fight when she chooses to console Ephram against Colin's wishes.

Andy is concerned that Ephram needs more extracurricular activities to get into a top college, but Ephram is only focused on his Julliard audition, which has surprising results. Amy's lack of interest in college preparation alarms her mother more than her father. Bright's poor grades get him kicked off the football team, threatening the scholarship his father believes may be his only chance to get into a decent school. Meanwhile, Andy tries to help a cheerleader (guest-star Kristen Bell) with ruptured breast implants, who cares more about looking good than her own health.

Andy's well-intentioned plan to give Ephram more free time by hiring college student Madison Kellner (guest star Sarah Lancaster) as a caretaker for Delia ends up making things worse when Madison treats Ephram like a child, as well and embarrasses him in front of Amy. Meanwhile, Andy's concern for Colin's alcoholic father (guest star Michael Flynn) blinds him to Nina's struggles with her divorce proceedings. Dr. Abbot continues to clash with his sister, Dr. Linda Abbott, when she tries to take over his office and the difference in their personalities and medical philosophies becomes alarmingly clear.

Amy moves back home, but finds adjusting to her old life difficult, especially after her parents (Tom Amandes and Merrilyn Gann) discover she's taking birth control pills and her former friends give her the major cold shoulder. Elsewhere in Everwood, Ephram thinks Madison is going to break up with him and Andy testifies on behalf of Nina as she and her recently out-of-the-closet ex-husband (guest-star Dylan Walsh) battle for sole custody of their son.

Ephram and Amy decide to go to prom together as friends, but Amy can't get up the nerve to tell Ephram that she has feelings for him after they run into his ex-girlfriend Madison and Amy realizes that he's still nursing a broken heart. Meanwhile, Linda decides it may be time to leave Everwood behind, and Andy's mentor, Dr. Donald Douglas (guest star Philip Baker Hall), asks him to perform risky brain surgery on a patient who turns out to be Dr. Douglas himself.

When Amy accompanies Ephram to his Julliard audition in Boulder, a romantic moment leads her to confess her newfound feelings for him. Meanwhile, Andy struggles to convince his mentor Dr. Douglas (guest-star Philip Baker Hall) that he needs even riskier brain surgery than originally thought and that Andy is the man to do it. Dr. Abbott faces losing his medical practice after it appears no company will insure him. Lastly, Bright decides not to attend his graduation ceremony, much to the disappointment of his family.

At her father's suggestion, a heartbroken Amy is determined to make the most of her senior year in the wake of Ephram returning from New York and telling her that piano has to be his number one priority. Andy contemplates telling Ephram about Madison's (Sarah Lancaster, who does not appear in the episode) pregnancy. Meanwhile, Rose naively agrees to help Bright find his true calling after she discovers that he hasn't enrolled for college classes and is in fact leading a life of total leisure.

Also, Dr. Jake Hartman (Scott Wolf) creates a marketing blitz for his new practice that threatens to push Dr. Abbott over the edge. Lastly, Nina takes in her friends' teenage daughter, Hannah (Sarah Drew, "Radio"), and asks Ephram to take her under his wing.