Meredith, shattered by revelations, is forced to work with Addison, Joe collapses at the bar, Cristina has some pretty shattering news of her own, and Alex starts working on Izzie.
After a fatal car accident, a man, a woman and their son are patients in the Seattle Grace hospital. The injuries of the mother reveal a family secret. Another patient has swallowed something strange, but refuses to reveal what. On the personnel level, Meredith and Cristina try to get along with the ending of their relationships. While Meredith tries to avoid Shepherd, Cristina and Burke are involved in the same medical cases. George feels uncomfortable still working with Olivia, who wants him to forgive her. Derek also reveals why he left New York.
Meredith's mother is admitted to the hospital, revealing that the once great surgeon now has Alzheimer's disease. Menwhile, Christina faints during operation and needs immediate care. She loses her baby due to complications and becomes a patient. Burke finally finds out about her pregnancy when it's too late. Mrs Grey gives hell to George because she thinks he is her husband, but George copes with it.
A storm rages in Seattle. Izzie is very disappointed by her date with Alex, and Meredith is upset with Derek. They both complain to George, which drives him crazy. At the hospital, Cristina has a patient that uses porn as a pain killer and Meredith takes care of an Asian girl who needs to see a Shaman before surgery. There is a power shortage and George and Alex are stuck in an elevator with a critical patient. They need to perform heart surgery, but Alex is too freaked out and so George does it.
A train wreck brings multiple casualties to Seattle Grace, leaving Meredith hanging for her answer. Meanwhile, Alex finds working without his "mojo" a disheartening experience, and Yang searches high and low for a missing appendage.
Addison and Derek go to marriage counseling. Derek says that he's finished with Meredith. Meanwhile, Meredith becomes the main gossip topic in the hospital and Izzie and Christina discover a pregnant man. Preston tells the Chief about him and Christina and Alex finally kisses Izzie.
Friends of Derek and Addison come from New York for a preventative surgery that causes discord among both couples. George helps a man who falls from a roof. Bailey delivers news to the Chief.
Thanksgiving sends the occupants of the house in different directions: Meredith escapes to the hospital, George goes hunting with his family, and Izzie throws a dinner that it appears no one is coming to.
Meredith's one night stand causes complications when he shows up at the hospital with an embarrassing problem, Burke tries to push Cristina toward the next step, and Alex's problems affect his performance.
The mother of the quints blames herself, Izzy becomes attached to her patient, Karev must face the consequences of his actions, and Cristina cares for an inmate desperate to stay at the hospital.
Izzie realizes that she is attracted to her patient with a heart condition. George treats Bex, a hermaphrodite. Meredith's mother gets a special visitors. Derek and Addison's relationship is still rocky.
The nurses strike, leaving the doctors unprepared for their extra duties. Cristina and Burke have to define their work relationship, Izzie relates to a pregnant teenager, and Meredith finds parallels to her mother in a case requiring her to remove life support.
The lives of everyone in the OR are threatened when a patient enters with a bomb inside of him... and a young paramedic with her arm inside the cavity is the only thing keeping it from going off.
While the man with the bomb lodged in his chest remains in Burke's OR, Bailey's injured husband remains in Derek's. Meanwhile, Bailey still hasn't delivered her baby.
Derek and Addison are shaken by the arrival of someone from their past. Meanwhile, Burke learns Cristina's secret, and Meredith delves into her family's dirty laundry.
Cristina babysits for Bailey and doesn't take to it well at all. Meanwhile, Addison and Derek come to terms with their relationship, and Denny keeps coming between Alex and Izzie.
A complication from the LVAD surgery puts Denny in the OR during a death cycle, Cristina maneuvers to get George kicked out, and an old mentor of the Chief's is admitted for treatment.
George begins to overstay his welcome at Burke and Cristina's apartment. Cristina takes a seminar and discovers that Chief Webber is taking it too. Meanwhile, Meredith learns a startling secret about her father, Bailey worries her colleagues will not treat her the same now that she's a mother, and Alex gets a lesson in bedside manners.
While Izzie grills George about the personal details of his life, Addison takes Alex to task about a sensitive case. Also, Burke feels the pressure when he treats his musical hero, and Meredith considers dating a hunky vet.
The struggle to get Denny a heart continues. Christina gets to run her own trauma. Shepherd is responsible for a friend's life. The Chief's niece is brought to the ER by his wife.
The chief tries to determine who's responsible. Callie presses George about his feelings. Derek and Meredith have to make a decision about Doc. The interns are charged with pleasing the chief's niece.