The "Who's the Boss," "Melrose Place" and "Charmed" star, will be one of four leads in the remake. The series, adapted from a British drama of the same name, revolves around four friends with turbulent romantic lives. Milano's character is Savannah, a successful -- and married -- lawyer who begins an affair with a handsome law partner. Her role appears to be the counterpart of the character played by Orla Brady in the original BBC format, which also starred Sarah Parish, Sharon Small and Shelley Conn.
Other stars casted for the remake include Yunjin Kim, Rochelle Aytes and Jes Macallan for the lead roles.
The show has been adapted by Gossip Girl writer KJ Steinberg, who previously created The Nine.
Mistresses is scheduled to premiere in the Summer of 2013.