Andy puts his foot in his mouth by picking a fight with Everwood's patron saint, Amanda Hayes (Anne Heche), who, unbeknownst to Andy, has been caring for her profoundly disabled husband (guest-star Jason Beghe) for the past five years. Meanwhile, Jake surprises Nina by asking her out on a date; Ephram and Bright realize their friendship may have grown too far apart to salvage; and neurotic-as-ever Dr. Abbott struggles to come up with a medical invention after learning that Dr. Brown and Dr. Hartman have successful inventions of their own.

Andy worries that Ephram is beginning to question himself and his chances of getting into Julliard after he applies to a college in Colorado as a back-up plan. Similarly, Harold has concerns of his own when Amy informs him that she's not applying to the school they always dreamed of her attending, Princeton, because it would take her too far away from Ephram. Meanwhile, Andy jumps head first into helping Amanda (guest-star Anne Heche) and her disabled husband (guest-star Jason Beghe) with a new therapy involving music, but it may be too much and too fast for Amanda; and Edna and Irv's marriage hits a rough patch after Irv loses his job and they contemplate their future together.

Ephram seeks guidance from his and piano mentor, Will Cleveland (guest-star James Earl Jones) when he's struggling to select the music program for his Julliard audition tape. Things don't go well for Ephram as he faces losing one of the most important relationships in his life after he accidentally hurts Will's feelings. Meanwhile, Bright takes a job working at the restaurant, "The Firehouse" where he meets waitress Serena. Things go bad though when they get caught by their boss in the most compromising position in the closet.

Lastly, Andy and Amanda experience a miraculous breakthrough in their music therapy with Amanda's husband (guest-star Jason Beghe), but Andy quickly questions the results.

Amanda decides to send her husband to a very nice treatment facility causing Andy to collapse as a result of stress and guilt over what has happened between him and Amanda. Meanwhile, Amy continues to give Ephram the cold shoulder for lying about Madison, Also Edna builds a writing room for Irv.

Andy and Amanda (guest-star Anne Heche) decide that it's time to tell Delia and Charlie (guest-star Shane Haboucha) about their relationship before they hear about it elsewhere, but Charlie's emotional reaction makes them question what they're doing. Meanwhile, when Hannah (Sarah Drew) doesn't jump at the opportunity to go on a date with a really cute guy, Topher, from school, Amy is convinced that Hannah is misguidedly saving herself for Bright.

Nina questions whether Sam (guest-star Jimmy Bennett) is going to be hurt again if her relationship with Jake (Scott Wolf) doesn't work out. Lastly, we flashback to Amanda (Anne Heche) and John earlier in their marriage of a more happier time with their son Charlie, right before he has his stroke.

Just as they've become somewhat comfortable with their new relationship, Andy and Amanda receive word that Amanda's husband, John (guest star Jason Beghe), has experienced a miraculous breakthrough in his recovery. Meanwhile, Amy learns the truth about why Madison really left town, an elated Ephram is offered an audition at Julliard, Hannah questions whether she's emotionally prepared to take the test for Huntington's Disease, and Bright is accused of sexual misconduct in the workplace.