Mark Sloan and Lexie Grey's relationship became one of the most beloved pairings in the Grey's Anatomy universe. Despite the fact that many late-comers to the series like Jo Wilson, Nurse Bokhee, and the Mercy West transplants (April Kepner and Jackson Avery) have appeared on more episodes than both Mark and Lexie, their tragic ending has made the couple's love story all the more compelling. The on-again, off-again pair were apart more often than they were together, but something about the chemistry between actors Chyler Leigh and Eric Dane made Lexie and Mark's relationship an iconic pairing on par with Meredith Grey and Derek Shepard. But they're not on par with Denny Duquette and Izzie Stevens, just FYI — they are forever the One True Pairing.