After being blackballed by most of the surgeons, Meredith uses Lexie to spark Derek's interest in her patient's rare brain tumor case and, in secret, gives guidance to April with Bailey's clinical trial; Callie's wish for Arizona and Mark to form a friendship comes to fruition and she realizes it's more irritating than helpful; Alex and Teddy research alternative surgeries for a very superficial patient; and Callie and Cristina struggle with a very difficult spinal surgery.

The doctors become nostalgic when George O'Malley's mother, Louise, returns to Seattle Grace for medical help after a botched surgery at a neighboring hospital; the residents are inspired by a medical miracle when they witness a harvested heart that continues to beat outside the body; a new pediatric fellow excites Arizona and makes Alex feel threatened; Jackson lets his suspicions about Mark and Lexie interfere with his work; and Henry and Teddy have their first marital fight when he expresses interest in pursuing medical school.