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.

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.

Picks up where the last episode left off. Meredith attempts to work with Addison Shepard. George is pimped out to relay the hospital gossip back to Webber. Meredith and Cristina relate at Emerald City Bar about what dating their respective attendings is like. Cristina ponders her relationship with Burke while trying to make a decision. Meredith is devastated by the latest blow to her love life. Meanwhile, Joe the bartender collapses.

There's tension between Meredith and Addison. We find out why Derek and Addison aren't together. Bailey puts George on an impossible case. The rest of the interns operate on a family that was just in a car accident.

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.