Dr. Izzie Stevens (Katherine Heigl) was a surgical resident at Seattle Grace Hospital on the television series "Grey's Anatomy." She moved in with Dr. Meredith Grey (Ellen Pompeo) and Dr. George O'Malley (T.R. Knight) and they soon become best friends. Soon after starting her residency at Seattle Grace, Dr. Alex Karev (Justin Chambers), exposes the secret that she was a lingerie model and paid for medical school with the income from her modeling. Initially humiliated, she overcomes the embarrassment and finds strength in the adversity. However, she does still hold insecurity about herself professionally and in how people view her due to her attractiveness.
Despite this incident, Alex and Izzie develop a friendship which eventually develops into a relationship. This is short-lived, however, as Alex cheats on her with a nurse and she breaks up with him. Soon afterward she moves on to a relationship with Denny Duquette (Jeffrey Dean Morgan). Denny is a patient in the hospital with a serious heart condition. As his situation declines, Izzie spends more and more time with him.
Their relationship blossoms and Denny asks Izzie to marry him and she accepts. His heart condition reaches the point that he needs a transplant and she cuts his support line to increase his chances of being on the top of the transplant list. Her ploy works and he gets the heart transplant, but he dies shortly after from a stroke. Izzie is devastated by his death and quits medicine. She finds out she was left millions of dollars by Denny and uses it to created a free clinic in the hospital in honor of Denny.
When George begins dating Dr.Callie Torres (Sara Ramirez), Izzie does not approve. She begins to feel an attraction to George and they sleep together. They both try to keep this a secret from Callie, though she eventually finds out and leaves George. He and Izzie try to have a relationship, but soon realize they have very little compatibility and stop trying.
Izzie and Alex reignite their relationship, and things seem to be going well. However, Izzie is diagnosed with cancer and given a very slim chance of survival. She begins to have hallucinations of Denny. They find a brain tumor and remove it, but her condition worsens. Thinking she is dying, she marries Alex. During an operation on her second brain tumor, Izzie flatlined on the table. She managed to survive and is now cancer free.
After Izzie returns to her duties, she makes a critical error in a patient's care and is fired from the hospital. She blames Alex for the mistake and leaves town. When she returns, Alex breaks up with her for good. They eventually get a divorce and she no longer works at the hospital.
"You want to call me Dr. Model, that's fine. But just remember that while you're sitting on two-hunded grand of student loans, I'm out of debt."
"I'm not being arrogant, it's just, it's just kind of a fact. For a long time I made a career from my looks, so I get it, I'm a pretty girl. And not in a "from a certain angle" way, in an obvious way. It's the blonde thing and the big boobs thing, big boobs are a key to obvious pretty if you know what I'm saying."