Meet Meredith Grey. Daughter of famous surgeon Ellis Grey and currently a first year intern at Seattle Grace Hospital. On her first day, she meets her fellow interns: Cristina Yang, a highly competitive Stanford graduate. George O'Malley, a quirky yet warm hearted guy. Izzie Stevens, a former model who's always optimistic. Overseeing them is Miranda Bailey, dubbed by her coworkers "The Nazi". Meredith also gets a surprise when she realizes that her one night stand from the night before is her new boss.
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.
A bike race injures several people, one of whom is left brain dead. Cristina and Izzie want to use his organs for organ donation, but they find the organ harvesting process an emotional one. Meanwhile, George deals with an over-flirtatious patient, and Meredith has to deal with Izzie and George moving in, Alex showing off, and keeping Derek at arm's length.
Alex uses Izzie's modeling against her, and her last ad causes a patient to reject her care. Meredith finds parallels between a patient and her mother, and Christina must deal with a hospital-savvy patient.
Meredith realizes that she must take on a lot more responsibility when she is told that her mother needs to sign over all of her assets to her. Izzie prepares to have a party for her boyfriend Hank's visit, but the size of the party far exceeds her expectations. Meredith has her first heart surgery, during which she fears that she has accidentally damaged the patient's heart. Meanwhile, Cristina and Burke hit it off.
All of the interns are in awe when a woman comes in with a record breaking tumor, but it is so far advanced that the woman's prognosis is not good. Now that Bailey knows about Meredith and Derek's affair, their jobs are in jeopardy, and she strongly advises Meredith to end it. Meanwhile, Cristina and Burke's secret relationship gets more complicated, and when no one else can be reached, Izzie has to perform a major procedure on her own.
Derek and Meredith try to be discreet as they spend the night together at Meredith's house, but their haggard appearance speaks volumes to Bailey, who warns Meredith to end the relationship. Meanwhile, George suspects an anesthesiologist of drinking on the job, Alex treats a former competitor who now finds honor in self-mutilation, Izzie has to deal with a patient who won't let his girlfriend go, literally, and Cristina battles a case of what seems to be the flu.
Meredith grows increasingly dissatisfied with fact that she knows nothing about Derek's life. Meanwhile, Alex treats a patient whose religious beliefs jeopardize her chances for recovery, and Izzie contemplates reconnecting with her estranged mother. Also, a pregnant woman in her 40s who's been diagnosed with cancer disagrees with Cristina's medical advice. And the interns are mystified by a patient who's being treated for seizures and who thinks he's psychic.
A sexually transmitted disease breaks out and affects several members of the hospital staff. Meanwhile, Webber reluctantly tells Derek about his own medical concerns. Izzie and Cristina worry about a patient's wife and daughter who can't agree on his care. Burke treats his college buddy Bill, whose medical diagnosis raises some questions regarding his wife's actions. And just as Meredith and Derek grow more intimate, a surprise from his past shows up.