A family is admitted after being involved in a car crash, but there is more to them than meets the eye. Meanwhile, Bailey and her team deal with a strange case, and relationship woes plague Meredith, Cristina and George.
Cristina is determined to get back to work, and despite not being fully recovered, she manages to crack an odd case. Meanwhile, Addison offers to help Bailey with a complicated surgery, and Alex receives important news.
A storm rages, causing power outages and jamming the elevator, trapping George and Alex inside with a vulnerable patient. Meanwhile, Meredith and Derek arrange a religious ritual for a young woman, and Cristina deals with an unusual case.
A train wreck brings in multiple casualties, leaving Meredith hanging for her answer. Meanwhile, Alex finds working without his mojo a disheartening experience, and Cristina searches high and low for a missing appendage.
Derek reluctantly attends marriage counseling with Addison, while Meredith, Izzie and Cristina steal a patient with an unusual problem. Alex helps a young patient gain her independence, and Cristina thinks Bailey knows about her and Burke.
Friends of Derek and Addison come from New York for a preventative surgery that causes discord among both couples. Meanwhile, George helps a man who has fallen from a roof, and Bailey delivers news to the Chief.
Thanksgiving sends the occupants of Meredith's house in different directions: Meredith escapes to the hospital, George goes hunting with his family, and Izzie throws a dinner to which it appears no one is coming.
Meredith's one night stand causes complications when he shows up at the hospital with an embarrassing problem. Meanwhile, Burke tries to push Cristina toward the next step, and Alex's problems affect his performance.
The mother of the quints blames herself. Meanwhile, Izzy becomes attached to her patient, Karev must face the consequences of his actions, and Cristina takes care of an inmate desperate to stay at the hospital.
Christmas hits Seattle, with Izzie caring for a man who fell from his roof while hanging decorations. Meanwhile, Cristina helps perform a heart transplant on a depressed boy, and George has to contend with the family from Hell.
Izzie becomes attracted to a male patient with a heart condition, and George treats Bex, a hermaphrodite. Meanwhile, Meredith's mother receives a visitor, and Derek and Addison's relationship is still rocky.
Meredith must choose between her dog and her roommates. Meanwhile, George deals with an elderly patient who has outstayed her welcome, Bailey's pregnancy has complications, Alex gets his exam results, and Richard has a strike on his hands.
The nurses are striking, and George refuses to cross the picket line. The interns are surprised by Bailey's seemingly immature replacement, Izzie connects with a pregnant girl, and an elderly woman's plight pushes Meredith to the limit.
While the man with the bomb lodged in his chest remains in Burke's OR with Meredith's hand in the cavity, Bailey's injured husband remains in Derek's. Meanwhile, Bailey's distress puts her unborn baby at risk.
Derek and Addison are shaken by the arrival of a figure from their past. Meanwhile, Burke learns Cristina's secret, Izzie deals with a very unusual case, Meredith delves into her family's dirty laundry, and George pours his heart out.
Cristina babysits for Bailey and does not take to it well at all. Meanwhile, Addison and Derek come to terms with their relationship, George connects with Callie, and Denny continues to come between Alex and Izzie.
Superstition strikes, with the interns convinced a series of deaths will occur. A complication from the LVAD surgery puts Denny in the OR, Cristina plans to make George move out, and Richard's old AA sponsor is admitted for treatment.
Cristina is desperate for George to move out of the apartment, while Izzie is jealous of Callie's relationship with him. Meanwhile, Cristina and Richard are rivals in a surgery seminar, and Meredith discovers a secret about her father.
Meredith considers going on a date with Finn, and Izzie tries to find out more about George and Callie. Meanwhile, Alex clashes with Addison over a sensitive case, and Burke is nervous about operating on a patient who is one of his heroes.
The victims of a serious car accident are admitted, with every surgeon required to help. Meanwhile, Callie's forwardness grates on Izzie, Addison makes Alex suffer, and Derek takes his frustration out on Meredith.
Richard is determined to discover the guilty party, and punishes the interns by making them arrange a prom for his niece. Meanwhile, Callie presses George about his feelings, and Derek and Meredith have to make a decision about Doc.