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.

While George is feeling a little less masculine because of the way Izzie and Meredith have been treating him (like a sister), Izzie is assigned to a patient about to loose all of his masculinity. Cristina, true to her competitive spirit, shows up early and assigns herself to an ill woman, who happens to have been Meredith's moms scrub nurse. Alex, meanwhile, is busying himself copying and pasting pictures of Izzie's racy magazine spread all over the interns' locker room. And while Meredith is trying to cope with her mother's Alzheimer's, Derek treats a patient who has managed to get nails stuck in his head.

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. As Izzie prepares to have a party for her boyfriend Hank (the scale of which is unknown to Meredith), Meredith has her first heart surgery. During the surgery she fears that she has fallen asleep and damaged the patient's heart. Meanwhile, Cristina and Burke hit it off. At the party, Meredith and Derek get caught together by Dr. Bailey.

Izzie tries to get George to find the courage to ask Meredith out. 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 advises Meredith to end it. Meanwhile, Cristina and Burke's secret relationship is also getting more complicated...

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.

Train Wreck victims come to Seattle Grace and all staff gets called in. Everyone deals with really weird cases. Except Addison and Izzie. They work with a woman who is pregnant.

Cristina, Izzie and Meredith take care of Shane, a man who appears to be crazy and claims that he is pregnant. Shane's case induces a spreading fascination among the staff. George relates to a patient's husband.

Derek learns one of Addison's secrets. Bailey talks about motherhood and depression to a mother who is set to have cancer surgery and who seems to not care about any decisions concerning the future. A resident is fiercely questioned about the death of a male patient. An ex-couple meet before lunch and get stuck - Meredith and Addison work on their case. Things get awkward when the ex-couple's daughter, Michelle, arrives at the hospital.

After a burn victim unexpectedly dies in the midst of a chaotic ER, the Chief and board member Jennings interrogate the residents to find the culprit, as all the Mercy West and Seattle Grace resident defends their actions in an effort to save their jobs.

After learning of Richard's drinking problem, Derek confronts him for the sake of his friend and the hospital, Izzie returns, hoping to reconcile with Alex, and tensions run high between Teddy, Cristina and Owen in the aftermath of Cristina's startling confession.

It's Valentine's Day, and the doctors must treat dozens of injured people after the roof collapses at a popular romantic restaurant; Derek tries to manage his busy schedule as Chief of Surgery; Meredith wrestles with her new duties as the Chief's wife; and Mark and Callie team up to convince Sloan to do the right thing for her baby.

When Teddy's patient seeks to end treatment and her life, she turns to Hunt for help. The situation triggers Hunt's memories of his life at war and his past relationship with Teddy. Meanwhile, Callie and Arizona have a difference in opinion on what their future holds, and Richard tries to adjust to his role as a surgeon.

Seattle Grace Hospital is hit with a crisis like no other in its' history.

Meredith, looking to prove she is Chief Resident material, learns that anything and everything can happen in an hour's time when she steps up to run the ER for a night; meanwhile, Bailey sneaks off with Eli and gets into a little mischief, and everyone is surprised when the Chief's wife, Adele, shows up as one of the ER patients.

The hospital gets inundated with flu infected patients, which causes the doctors to slowly fall ill one by one. Derek must fight off the sickness as he prepares to give a speech on brain mapping and the residents place bets on who will fall ill first. Meanwhile, a new doctor at the hospital gives Alex a glimpse into an alternate form of medical practice.