Cristina is bothered by a new year's mandatory work limit. Izzie patient, Denny Duquette, wants two things: 1. a heart transplant, 2. Izzie. Addison detests Derek's trailer, Derek visits Meredith's mom, George treats a young teen hermaphrodite frustrated by her pre-pubescence. Other news includes patients doing uncanny things and relationship havoc being wrecked between the doctors, as per usual.

Cristina gets to scrub in on a rare surgery which incites envy. Alex questions his future in plastics. George and Addison work together with Noelle. Noelle is pregnant with twins but one of them is growing slower than the other. Her fiancé has problems of his own. Derek's sister visits. A patient's wife makes things hard on the staff since she has made her husband's health her job. A woman's sexual exploits are questioned.

Meredith works furiously to save a paramedic trapped in an ambulance; Lexie holds the life of a patient in her hands; Derek must rely on a nurse to save a patient; Bailey struggles to balance her personal life with her work.

After his fellow surgeons try and fail to bring Derek back to work, Meredith must summon the strength to convince him. Meanwhile the hospital is abuzz as Mark attempts a rare face transplant surgery. Cristina, at last awarded her first solo surgery, is more focused on the needs of her friends, and Izzie does her best to keep her medical condition a secret.

A generous 25 million donation is offered to Seattle Grace by the parents of Arizonas 10-year-old patient, she finds herself in a conflict of interest when his condition worsens. Cristina tests her boundaries with Owen at the hospital. Alex is left with all of Izzies hospital bills to contend with.

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