Izzie Stevens, played by Katherine Heigl, is excited about her position as an intern at Seattle Grace Hospital. She is upset when people talk and whisper about her when her underwear ads hit the magazines, but she takes charge when she strips in the locker room and points out that while they have tons of medical school debt she is debt free.
Izzie moves into Meredith's house and begins dating Alex. She falls in love with Denny, a heart patient at the hospital. She makes the hard decision to cut Denny's LVAD wire to get him further up on the donor list and get the available heart, but things don't go as planned because Burke gets shot and doesn't show up. The interns are able to save Denny and he gets his new heart, but dies a couple of days later and Izzie is devastated.
After several months, Izzie begins dating Alex again, but when a heart patient comes in that reminds her of Denny, she starts thinking that she's seeing Denny. He says he is there for her. She even carries on a relationship with him and finally understands that he is there for her because she is going to die. Izzie decides to fight to live and goes about trying to figure out what is wrong with her. She discovers that she has cancer.
When things are pretty bleak for Izzie, Derek and Meredith give up their wedding so that she and Alex can get married. She recovers from brain surgery and then leaves, not telling Alex or anyone where she is. When she returns, Alex tells her that he is happy that she is cancer free, but he deserves to be treated better than how she has treated him, so she leaves again.