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Mark returns during season three at Addison's drunken behest, but she again rejects him once sober.
Undeterred, Mark sells his successful private practice (which he previously shared with Derek) and takes over the plastics program at Seattle Grace Hospital.
Though Lexie initially declines, he remains committed to their relationship, and she agrees early in season six.
Mark's focal storyline in the series involved his romantic relationship with Lexie Grey (Chyler Leigh), one of the interns who was on his service when they started dating.
It is eventually revealed that he and Derek grew up together and that he, having lost his mother as a child and emotionally neglected by his father, considered Derek's mother as his maternal figure.
As he was an only child and Derek was the only son, they became close friends and he was Derek's best man at the latter's wedding to Addison.
When Addison shows up at Seattle Grace for a case, Mark attempts to sleep with Addison again but she refuses.
The nurses later start a club against him called Nurses United Against Mark Sloan.
During Meredith's morphine rampage, Mark finds out about his nickname Mc Steamy which was given to him by her during his first trip to Seattle back when he attempted to get Addison back and earn Derek's friendship back.