On the morning of her first day as a surgical intern at Seattle Grace Hospital, Meredith Grey is running late as she recovers from a one-night stand and prepares for her first day. Meredith quickly befriends George O'Malley, who's quirky, yet lovable, Cristina Yang, a highly competitive woman, and Izzie Stevens, a model turned surgical intern. Each of the new interns get assigned to Dr. Miranda Bailey, who past interns have dubbed "the Nazi".

Meredith's first patient, a young beauty pageant contestant, recently began having severe, life-threatening seizures and Meredith uncovers that she'll need brain surgery to save her life. However, things take a turn when the neurosurgeon, Dr. Derek Shepard, happens to be Meredith's one-night stand. He wants their brief relationship to progress into something more, but Meredith is firm on her stance - their relationship should remain strictly professional.