An eighteen-year-old girl comes into Andy's clinic to be checked for breast cancer because it runs in her family. When the results come in, the girl and her older sister, who has had a double mastectomy due to breast cancer, return to see them. Meanwhile, while out on a date, Bright and Hannah are forced to call Harold after something happens to the both of them and Kyle tells Ephram that he no longer wants piano lessons.
Dr. Andy Brown's seemingly perfect life was shattered when his wife, Julie, was killed in a tragic car accident. Prior to the accident, Andy was a world-famous neurosurgeon who often put his career before his family life. Now, Andy must single-handedly raise his two children, Ephram and Delia. In order to do so, Andy moved his family from New York City to the quiet, yet charming town of Everwood, Colorado.
In Everwood, Andy opened a free clinic, much to the dismay of most of the citizens. However, Edna Harper saw something in Andy that no one else saw and applied to be Andy's nurse and office manager. Andy was also well received by Irv, Edna's husband, and his new next-door neighbor, Nina Feeney. But along with the warm welcomes came the less than pleased individuals, including Dr. Harold Abbott, who forbade his wife Rose, and children, Amy and Bright to be around Andy or his children.
But regardless of such warnings, Amy quickly befriended Ephram, who instantly fell in love with her. Over the years, the two have formed a friendship, and for awhile, they even managed to be more than just friends. Ephram also formed an unlikely bond with Bright, and the two remain close friends, and recently have become roommates. Over time, Harold warmed up to Andy, and the two are now partners. However, despite the picturesque appearance of Everwood, the residents are faced with hardships and drama, including cancer, drug addiction, secret affairs, and tragic deaths all while trying to live a quiet life in a small town.