The series opens with Meredith removing a sofa pillow from the bare bottom of a man named Derek. The evening before, these two had downed a few drinks and ended up sleeping together at Meredith's mother's house, which she's trying to sell - a fact she spits out to Derek before politely asking him to leave so she can get ready for her first day at work.

Arriving as a surgical intern at Seattle Grace Hospital, Meredith is assigned to the "nazi," Dr. Miranda Bailey, as her resident. Joining our pretty protagonist in this assignment are Cristina Yang, Izzie Stevens and George O'Malley. Meredith's first case is a beauty pageant contestant suffering from seizures. When a surgical consult is called down, guess who the attending physician is? Derek. Or, to be more precise, Dr. Derek Sheppard. He wishes to talk to Meredith, but she's determined that it was a one-night stand to be forgotten about entirely.

As the first day wears on, Cristina and Meredith bond. Izzie is stuck with rectal exams because she gets on Bailey's wrong side , while George is chosen by Dr. Preston Burke to assist on a surgey. He doesn't perform very well, however, as the patient dies and another arrogant intern, Alex Karev, dubs George as "007" because he has a license to kill.

Meanwhile, Meredith comes across the Chief of Surgery, Dr. Richard Webber. He used to work with her mother, the famous Ellis Grey. The other interns are impressed by the status of Meredith's mother - and afraid that the younger Grey been riding the medical coat tails her well-known matriarch. When the hour ends, however, we see Meredith's visiting a nursing home ... to spend time with her mother, who has Alzheimer's Disease.