Izzie becomes attracted to a male patient with a heart condition, and George treats Bex, an intersex patient. 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.
Everyone reminisces about the past. Meanwhile, Izzie is emotionally devastated, with the others trying to help her, Adele gives Richard an ultimatum, and George and Derek are put in quarantine when an outbreak of the plague is suspected.
Izzie copes with her grief by baking furiously, and George has to deal with an obstinate patient. Meanwhile, Meredith must choose between Derek and Finn, Addison drowns her sorrows in alcohol, and Cristina meets Burke's difficult mother.
Izzie returns to the hospital, but finds it difficult to go inside, and George is tired of Callie's presence at home. Meanwhile, Addison cannot seem to get rid of Mark, and Cristina tries to cope with caring for Burke.
Meredith becomes a patient, and Derek and Addison are equally angry at Richard for allowing Mark to join the staff. Meanwhile, Izzie receives a visit from Denny's father, and Burke is plagued by doubt over his ability to return to surgery.
Izzie returns to the hospital under probation, and George tries to make amends with Callie. Meanwhile, Cristina's deletion of Bailey's name on Burke's OR board makes her assume he is against her, and Derek's irritating sister Nancy visits.
Derek, George, Alex, Burke, Richard, Joe and Walter go on a camping trip. Meanwhile, Meredith assists Mark with gender reassignment surgery, Izzie avoids discussing her grief, Addison works with Callie, and Cristina feels Bailey's wrath.
George must deal with his family's presence when his father is admitted. Meanwhile, Burke's secret is almost out, Alex tries to get close to Izzie again, and Richard comes to a decision about his marriage.
A traumatic car accident fills the ER. Cristina has a crisis of conscience about her deceptive teamwork with Burke, Izzie pushes the boundaries of her probation, and Callie tries to explain herself to George.
Bailey is adamant that Burke and Cristina should be punished, Derek doubts his abilities, Izzie tries to take a stand against Mark's patronizing behavior, and Meredith deals with family in two very different ways.