Mixed connective tissue disease (MCTD) is believed to be incurable and seems to have a variable prognosis. Some patients have a mild self-limited disease, whereas others develop major organ involvement that requires aggressive treatment. Because no controlled clinical trials have been performed to guide therapy in MCTD, treatment strategies must rely largely upon the conventional therapies that are used for similar problems in other rheumatic conditions (systemic lupus erythematosus, scleroderma, polymyositis). Given the heterogeneous clinical course of MCTD, therapy should be individualized to address the specific organ involved and the severity of underlying disease activity. Corticosteroids, antimalarials, methotrexate, cytotoxics (most often cyclophosphamide), and vasodilators have been used in the treatment of MCTD with varying degrees of success.