But some fans can't quite picture the "Two and a Half Men" comedian as the supervillain.
Especially since most of us still think of him as underdog Duckie in "Pretty in Pink."
Cryer will make his first "Supergirl" appearance in the 15th episode of the current season and will be a recurring character.
"We are enormous fans of Jon Cryer, and he was instantly our dream actor to play the iconic role of Lex Luthor," said "Supergirl" executive producers Robert Rovner and Jessica Queller. "Jon is a super-talent, and the fact that he played Lenny Luthor in 'Superman IV' brings an added layer of legacy to his casting. We’re beyond thrilled to welcome Jon to the Supergirl family."