Andy meets with Colin's parents to discuss a potential course of treatment for the comatose teen. Amy is heartbroken and Ephram is furious when Andy decides against performing a risky operation on Amy's comatose boyfriend. Meanwhile, Delia is forbidden from playing with her only friend, Magilla (guest star Bret Loehr), after his parents discover them playing dress up. Dr. Trott, a traveling psychologist (guest star Jane Krakowski) sets up shop and stirs up the emotions of several townspeople who seek her guidance, much to the chagrin of a distrustful Dr. Abbott.

The former Big Apple neurosurgeon, Dr.Andrew Brown, puts on his scrubs for the first time since he relocated his family to Colorado to operate on Amy's comatose boyfriend, Colin (Mike Erwin), with the help of his friend and surgery partner from New York, Dr. Brian Holderman (guest star Lamont Thompson). Adding to his performance anxiety is the identity of the patient---Colin Hart, the boy who was dating Amy before she stole Ephram's heart.

It also doesn't help that the tricky procedure he plans to perform has never been attempted before. Amy leans on Ephram for support as she awaits the outcome. Meanwhile, an emotional Bright breaks down and admits what actually happened the day of the car accident as Colin's former life in Everwood is also revisited as flashbacks reveal some startling secrets about the teen's last days before the accident that put him in the hospital.

A heartbroken Ephram finds himself the odd man out as Amy prepares for Colin's homecoming. Meanwhile, Andy and Dr. Abbott join the town in a debate over the use of medicinal marijuana after a large quantity is discovered in a deceased woman's greenhouse; and Andy provides medical guidance to Nina after her son's teacher suggests she put him on Ritalin.

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.

Resentful at being forced to accompany Andy and Irv to a remote lake cabin, Ephram takes a small boat out alone and his inexperience leads to a serious accident and a night of terror for Andy. Meanwhile, Colin and his parents must decide whether to allow Dr. Brown to perform a second dangerous surgery; and Nina confronts her husband Carl after she accidentally discovers he is having an affair.

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.

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.