Meet Meredith Grey. Daughter of famous surgeon Ellis Grey and currently recovering from a one-night stand. She shoos away her evening's companion, saying she'll be late for her first day of work. She is a first year intern at Seattle Grace Hospital and is working alongside some colorful characters. Cristina Yang is a highly competitive Stanford graduate who befriends Meredith. George O'Malley is a quirky warm hearted man who learns a lesson or two on his first day. Izzie Stevens is a former model who doesn't get any special treatment on her first day. And Alex Karev is an arrogant jerk who misdiagnoses a patient on his first shift. Overseeing them is Miranda Bailey, (not-so-) affectionately dubbed 'The Nazi'. Meredith also gets a surprise when she realizes that her friend from the night before is a co-worker, and even worse, her boss.

A bike race injures several pedestrians as well as well as participants. One pedestrian is left brain dead. Christina and Issie wish to use his organs for organ donation but with Christina's detachment and Issie's ever hopeful attitude that the man will recover, they will find the organ harvesting process an emotional one. Preston faces feelings of his dislike of organ harvesting - as a surgeon, he likes saving lives; harvesting organs doesn't save the person's life. George deals with Mac, a friend of the chief, who won't stop flirting with him. He is in need of a new liver. Meredith is fed up with Alex showing off as she continues trying to push Derek away. She also is reaching the limits of Issie's sunshine and George's politeness as she goes on living with them. Then there is their desire to see Meredith's mother's medical tapes. Getting through the day, Meredith realizes the keys to winning the race.

As Cristina tries to recover, she proves to be a very difficult patient, and a visit from her mother doesn't improve her demeanor any. And Meredith's mother, Dr. Ellis Grey, has the hospital staff running in circles.

Meredith tries to avoid the Shepherds. Cristina and Burke go out on a date and end up getting caught up in their jobs. Derek asks Meredith not to ignore him until Addison comes walking around the corner.

The holiday season has started but not everyone is in a festive mood. This is Alex's last day in the hospital unless he passes his boards practical exam the next day, thus everyone helps him to review so that he succeeds. However, Izzie is not happy about the others helping him and Meredith has to remind her of the true spirit of the Christmas holiday. Justin is in need of a new heart. One is available but he does not want it because he does not believe Santa gave it to him as his mother said. Cristina and Burke, both handling Justin's case, have opposing views on the matter due to their different stances on religion. Despite a reconciliation with his wife, Derek isn't in a festive mood. George has a simple case of a woman who has a bleeding ulcer, he realizes that the ulcer is caused by her entourage but fails to keep them away, with the consequence that it perforates.

An explosive case arrives at the O.R. that might endanger all the lives of the people working there, which leads Dr. Burke to declare a "Code Black" for the hospital. Bailey worries where her husband is as she is in labor. Also Izzie and Alex may be creating some heat.

Derek is still operating when he finds out about Meredith's current situation. Meredith is freaking out about her situation. Webber and Bailey are dealing with medical health issues. Cristina and Izzie have their own issues to deal with because of Meredith's situation. Addison freaks out when George tries to find a solution to Bailey's impromtu postponement. Overall, Seattle Grace Hospital is still under code black and the situation is getting worse.