The surgical staff tries to be optimistic as a young woman clings to life after a brutal attack. Meanwhile Meredith puts her career on the line to save a newborn in the hospital nursery, and the other interns learn that it takes more than just medical knowledge to be good at their jobs.

Meredith grows increasingly dissatisfied with the unknown details of Derek's life. Meanwhile, Alex treats Devo, a patient whose religious beliefs jeopardize her chances for recovery; Izzie contemplates reconnecting with her estranged mother; Zoey, a pregnant woman in her 40s who's been diagnosed with cancer, disagrees with Cristina's medical advice; and the interns are mystified by Cable, a patient who's being treated for seizures and who thinks he's psychic.

After a series of deaths at the hospital some of the staff become very superstitious. Izzie worries about Denny and gets confronted by Alex. A patient with OCD drives Cristina crazy. Derek and Addison discuss their relationships with Meredith. Richard treats a friend from 17 years ago who reveals a secret about a dark time in his past that involves Ellis. George gets an earful about the women he's not talking to. Burke and Cristina argue about kicking George out.

It's Halloween at Seattle Grace! There may be jokes, pranks, and/or scare tactics. Some of the women form a club based on an experience they all share. A man volunteers for what most of the doctors believe is an unnecessary surgery. One of the patients is in the hospital because they tried to carve a pumpkin in an unconventional manner.

Alex returns to the hospital and discovers a lot has changed since he left. Meanwhile, Jo has to make a difficult decision on a case, and Arizona tries to distance herself from Eliza.