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.

The unannounced arrival of Jacob and Nonny Hoffman (Mark Rydell, Doris Belack) from New York is greeted with glee by Delia and Ephram. But Andy feels pressed to his limits as he tries to placate his overbearing guests, particularly his pushy father-in-law, who openly criticizes the physician's parenting skills. On top of that, Jacob obviously enjoys a special bond with Ephram that Andy can't duplicate. Meanwhile, Nonny makes her own impression in Everwood when she butts heads with Edna over Delia's affections. Lastly, Ephram sneaks out of the house to see Amy who is still emotionally recovering from the aftermath of Colin's (Mike Erwin) surgery.

Much to resident thespian Dr. Abbot's chagrin, Andy begrudgingly auditions and is offered the lead in Everwood's production of ""The King and I."" As Dr. Brown struggles with his lines, Ephram struggles with his emotions when his intense feelings for Amy are complicated by Colin's (Mike Erwin) desire to be his friend.

Approaching the anniversary of his mother's death, Ephram confronts a repressed memory of his father cheating on his mother, causing an even bigger rift between father and son that eventually leads to a firestorm of emotions. Meanwhile, Amy grows concerned that Colin might not be recovering as well as everyone thinks when he gets violently ill on one of their dates. Amy tells her father who later tells Doctor Brown which causes the Harts to dismiss Andy from being their family doctor and causes a feud between Amy and her father.

As the day of Colin's (guest star Mike Erwin) surgery approaches and emotions run high, Andy takes Ephram and Delia on a road trip to his old medical school to consult with his mentor, Dr. Donald Douglas (guest star Philip Baker Hall). Back in Everwood, Colin kidnaps Amy and Bright in the middle of the night to surprise them with a special day of memories and hopes for the future.

In the second season opener, the town of Everwood deals with the aftermath of Colin's unsuccessful surgery, as he is now dead. The Brown family begins to feel ostracized by the town due to Colin's death. Meanwhile, a saddened Andy feels guilty of not doing his very best as regretting now over his promise to Colin of not resuscitating him if the surgery goes wrong. Amy and the rest of the town find out about this matter and confront Dr. Brown over it.

When Andy invites Linda Abbott over for dinner to discuss a patient, Delia lashes out through foul language, but it is an enlightened Ephram who figures out the cause of his sister's bad behavior, thanks to insight provided by Madison (Sarah Lancaster). Amy's depression deepens, but when her therapist recommends medication, Dr. Abbott refuses to write a prescription to help his daughter cope with Colin's death.

Dr. Brown courts Linda Abbott despite Edna's and Harold's insistence that he's wasting his time, but Andy persists, forcing Linda to tell him that she is H.I.V. positive. Bright tells Ephram he can win Madison's affections by ignoring her, but the plan goes awry when she breaks up with her boyfriend. Amy meets a flirtatious and attractive town bad-boy, Tommy Callahan (guest star Paul Wasilewski), whose compassion for her problems touches her heart for the first time since Colin's death.

Ephram and Bright conspire to get Ephram a fake I.D. so that he can get into a bar to see Madison perform with her band. Meanwhile, Nina leans on Andy for emotional support after she is served with divorce papers, but the genuine affection between the two raises a red flag for Linda; Harold and Rose (guest star Merrilyn Gann) schedule a meeting with Amy's guidance counselor after receiving her less-than-stellar report card. Finally, Tommy (guest star Paul Wasilewski) takes Amy to a party where she finds closure over the loss of Colin (guest Mike Erwin), but the evening takes a life-threatening turn.

Ephram is on cloud nine after being accepted into Julliard's summer program, but his emotions are sent into a tailspin when Amy shares her feelings for him and asks that he stay in Everwood for the summer. Meanwhile, Dr. Abbott's family thinks he's gone off the deep end when he decides to open a bagel shop in response to losing his malpractice insurance, and Andy learns a shocking revelation about his family.

Ephram and Amy are reunited after a long summer spent apart while Ephram attended Julliard's summer program in New York, but Amy's euphoria is quickly replaced with paranoia after she notices Ephram acting distant. Meanwhile, Andy is plagued by guilt over whether he made the right decision concerning Madison's pregnancy, and Dr. Abbott befriends the town's newest citizen, Jake Hartman, who turns out to be a doctor from California looking to open a new practice in Everwood.

Amy and Ephram decide to meet at the Abbotts' Cabin to take their relationship to the next step as both parents on each side worry as they know their kids intentions. Although while there they realize they may not be able to handle it. Andy and Amanda chaperone Delia and Charlie on a date. Although the evening turns when Andy and Amanda begin to feel they are on a date. Lastly, Nina turns to Jake when Sam is hurt while ice skating and her feelings for him change.

Ephram prepares to leave for Europe as he feels that he has nothing left for him in Everwood. However, he's caught off-guard and questions his plans when Andy reveals the secret that Amy has been keeping from Ephram. Meanwhile, Nina and Jake contemplate going into business together, but the stress on their relationship proves a big obstacle to overcome. Meanwhile, Bright finally confesses he has feelings for Hannah.

With Ephram (Gregory Smith, who does not appear in the episode) gone and no longer feeling any significant ties to Everwood, Andy consults with Delia and contemplates accepting a prestigious position with a Chicago hospital. Uncharacteristically upset over this bit of news, Harold takes it upon himself to give Andy a reason to stay. Meanwhile, Jake moves in with Nina, causing Andy to question whether he should rock the boat by telling her how he really feels, and Bright finally admits his feelings to Hannah.

The fourth season begins with a nice wedding of an unexpected couple and kiss at the airport for couple Bright and Hannah in Everwood.

Nina finally chooses between the two men she loves - Andy and Jake while at Delia's behest. Amy develops a new friendship with college-age student Reid (guest-star Justin Bardoni) while waiting on her mother Rose at the hospital. Also, Amy and Rose find that Rose's cancer has driven them apart rather than brought them together. Bright flirts with a new girl who might become his roommate, but is more involved in knowing what girlfriend Hannah scribbled off the postcard that she sent to him. Lastly, Ephram makes an emotional return to Everwood just in time for an unexpected wedding.

Ephram reveals information about his dad to Nina that surprises her and adds a new twist to her inner Andy-or-Jake struggle; Andy finds more of a connection with his dad (guest star Charles Durning), who's still in town; Amy and Ephram recall a moment from their past that helps Amy realize that Ephram is always there for her. Lastly, Hannah and Bright come together as friends, realizing that there's still a close bond between them.

After their house has been sold, Nina and Sam temporarily move in with the Browns. Wanting to take care of an unresolved issue in his life before he can propose to Nina, Andy takes a mysterious trip. Bright learns that Hannah has received a scholarship to Notre Dame and is devastated at the thought that she may accept it. Edna upsets Harold and Rose when she reveals her plans to leave Everwood. Delia is thrilled with Andy’s belated Bat Mitzvah gift.