A traumatic car accident fills the ER. Izzie pushes the boundaries of her probation. Cristina has a crisis of conscience about her deceptive teamwork with Burke.

Recent events strain Burke and Cristina's relationship. Mark and Derek must work together when two close-knit brothers seek medical help. One of Meredith's half sisters is admitted to the hospital.

Meredith discovers that Derek has a problem sleeping while her father comes to visit the hospital. George's father is moving from one surgery to another. A patient named Heather checks into the hospital. Heather is 17 and has a nasty attitude that results from her medical condition and all the surgeries it has required her to have. Izzie has an emotional breakdown when she tries to hand over something very important to her. George's family comes to visit to celebrate his father's surgery. Cristina and Burke are playing Uncle.

Cristina and Burke continue to play Uncle until one of them gives in. Derek and Meredith are fighting over the reason for their sleepless nights. Meredith tries to talk to her father about his side of the story. There's tension between Alex and Addison. There is even more tension between Addison and Mark. Addison confides in Callie. Bailey wishes she didn't have to keep a secret from one of the interns. Callie rushes to be with George after she learns that his dad needs an emergency procedure. Izzie may have found 'some good to do' with her inheritance.

George has a surprise visitor. Bailey's family is falling apart. Derek sorts through what kissing Rose means. Meredith discovers something that doesn't inspire hope or happiness in her. Alex treats a faith healer.

The hospital staff is left to deal with the aftermath of George's passing. Hitting the staff hard, they all find unique ways to get through the various stages of grief. George's mom returns, faced with the difficult task of deciding what to do with his organs.

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