Lexie is the daughter of Thatcher and the late Susan Grey, and the younger half-sister of Meredith Grey. She also has a younger sister, Molly Grey Thompson. She is a graduate of Harvard Medical School.

Lexie is a new intern at Seattle Grace Hospital. She was introduced in the penultimate episode of the third season as the woman Derek Shepherd met at Emerald City Bar.

In the third season finale, Derek confesses to Meredith he met another woman (though he doesn't specify who) and when she asks if she should be worried, he confirms her fears. Lexie would make her first appearance in Seattle Grace when she introduced herself to George O'Malley, who realized her connection to Meredith.