Ephram returns to Everwood, and to Amy, after a summer in New York studying at Juilliard, but as happy as she is, she fears he has grown apart from her. Andy is racked with guilt over feelings that he may not have acted in the best interest of a pregnant Madison. Meanwhile, Dr. Abbott learns that the town's new resident has come from California to start his own medical practice.
Dr. Abbott convinces Amy to forget about Ephram and concentrate on having a great senior year acter Ephram finds out he failed his Juilliard summer program and tells her he must now focus solely on piano.
Ephram wishes he hadn't told Nina he would watch out for her new houseguest Hannah at school, as the ongoing task cuts into his time with Amy. Amy, on the other hand, comes to really like Hannah and forms a bond with her.
Andy realizes he has trouble with Delia's growing up when he has to answer her questions about the mysterious item, Nina's vibrator, she has stumbled upon.
Andy embarrasses himself when he gets into a war of words with Amanda Hayes, an Everwood resident who has been unselfishly devoted to her disabled husband for the last five years.
Ephram decides to apply to a local Colorado college to cushion himself in case he doesn't get into Juilliard, but Andy worries that he's slowly starting to doubt his own chances.
Ephram goes to Jake's office for an STD test, but when Jake coyly hints to Andy that his son has plans to become sexually active, Andy and Harold decide that they are going to convince Ephram and Amy that it's worth waiting for their first time together, which seems to work until Ephram realizes his casual chat with Andy was calculated.
Ephram prepares his audition program for Juilliard, but wrestles with which music to choose. When he turns to his mentor Will Cleveland, he only ends up damaging the relationship with some stinging words towards Will.
Ephram and Amy make plans to sneak up to her parents' lakeside cabin when they decide that they are ready for their first sexual experience together, but once there, find that the pressure is greater than either of them realized.
Andy tries to hand the case of Amanda's husband over to Harold Abbott when he fears he's becoming personally interested in Amanda. Bright and Ephram reconnect over Ephram's need for advice on whether or not he should tempt fate and try to see Madison when her band plays a gig at a local club. Meanwhile, Amy learns a startling family secret about Hannah and confronts her about it.
Amanda decides to send her husband to a top care facility, but upon learning this, Andy passes out and is taken to the hospital after bearing too much anxiety and remorse over his dalliances with Amanda. Meanwhile, Ephram is still in the doghouse with Amy over his long-hidden information about Madison, while a despondent Irv suggests that he and Edna try a separation.
Nina acts as a comforting shoulder when Jake's girlfriend from Los Angeles comes into town. Amid the insanity, she finds that a possible attraction still exists between her and Jake. Meanwhile, Andy inadvertently embarasses Delia before her hockey team, and Harold and Rose worry that Amy is setting her heights too high with her interest in a competitive ballet program in Denver.
Andy's strength of character is thrown into question when Nina witnesses the affair between him and Amanda. Meanwhile, Amy and Ephram coax Hannah to cut school for a day and bring Bright along with them, while Harold and Edna's feuding must be put aside when a medical crisis brings them together.
Andy and Amanda decide to tell their kids about their relationship, but Charlie's unsettling response makes the couple rethink their actions. Meanwhile, Hannah turns down a date from an attractive classmate which prompts Amy to think she is holding out for an uninterested Bright, while Nina begins to pull away from Jake, fearing the fallout from yet another inevitable broken romance will hurt her son, Sam.
Andy and Amanda get word that her husband, John, has had an amazing breakthrough in his recovery process, which puts a crimp in their burgeoning relationship.
Amy convinces Ephram that it would be better for him to take Andy to New York for his Juilliard audition while the couple sorts out recent events between them, but Andy is troubled over whether or not to tell him the truth about Madison. When Ephram inadvertently bumps into Madison in Manhattan, they decide to get together, but Andy decides to intervene and holds the information which could create a permanent rift between him and Ephram.
While in New York, Ephram meets up with Madison just before his Juiliard audition, only to be told that she was pregnant with their child when she left Everwood. The news sends him into a tailspin and could both affect the audition and alter his future. Amy, meanwhile, is left to wonder about what this will mean for her future with Ephram, while Dr Abbott helps a man cope with the imminent loss of his son after a hunting accident.
Ephram returns to Everwood following Madison's devastating news with a sense of confusion about the future, and turns to Amy's shoulder for comfort. Andy discovers, to his surprise, just how strong Nina's feelings for Jake are. Meanwhile, Bright coaxes Hannah into going out with a boy who has a crush on her.
A rattled Jake looks to Andy for advice when he is told by Nina's younger brother that he probably doesn't have a future with Nina. Meanwhile, when Amy learns she has gotten into Princeton, she presumes only her father could have mailed in the application and her attempt to get together with Ephram further casts a shadow over their relationship.
Ephram makes a major life-altering decision which creates heartache for Andy, as Ephram tries to make money to flee Everwood for Europe. Meanwhile, Nina is perplexed by Andy's recent change in moods around her, but Delia figures it out and confronts him about his long-gestating feelings for Nina. Meanwhile, Bright finds himself jealous when Hannah and Topher go to the prom together.
Ephram readies to leave Everwood for Europe, feeling like life and the people he knows there have nothing left to offer him. He is taken aback, however, when Andy spills some secret information that Amy has been hiding from him, and must decide whether or not to leave after all.
With Ephram in Europe, Andy considers a prestigious position at a hospital in Chicago. Harold tries to give Andy a reason to stay, while Andy mulls over telling Nina how he feels about her, even though she has just moved in with Jake.