Izzie Stevens had cancer. Alex married her and she survived. Then, it was kinda like everything just vanished in season six. After a brief return, she admitted that Seattle wasn’t her home any more. Later, Alex got sent divorce papers, and now we know Izzie secretly had Alex’s twins, lives on a ranch in Kansas, and became a surgical oncologist. 

Katherine HeiglThe reason for her departure was that she pulled out of Emmy consideration in 2008 because she felt the material didn’t deserve it. In 2010, her character vanished completely. Shonda Rhimes denied that she had ever wished to be able to return to her character in all the years. TVLine reported that she said, “I’m done” with this story in 2015. 

Heigl became a star in many romcoms, before returning to TV. SituationIf so, DoubtShe joined, as well as others, in recent years. SuitsAnd the 2020 series Firefly Lane.