As his wedding anniversary draws near, Andy loses all hope and questions whether he will ever feel his life is worth living again. Meanwhile, Ephram and Amy share their first kiss while on a field trip; and Dr. Abbott has a panic attack when his wife Rose(Merrilyn Gann) proposes they take salsa dancing lessons. Andy also helps a couple whose marriage problems are caused by hives.

In hopes of raising his little sister Delia's spirits, Ephram does his best to recreate his mother's Thanksgiving traditions as the Brown family spends their first holiday without her. Meanwhile, in order to save a patient's life, Dr. Brown must find the man's missing brother, who is believed to live in the woods; and curmudgeonly Dr. Abbott attempts to befriend the entire town when he has a health scare and questions whether anyone would attend his funeral.

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.