Chronic immune thrombocytopenic purpura (ITP) is characterized by macrophage destruction of platelets, primarily in the spleen, and occurs in both adults and children. Historically, splenectomy is often required, especially in adults with chronic ITP; however, several medical options have been used successfully prior to splenectomy or when this procedure has either failed or been refused by the patient. These include corticosteroids, intravenous immunoglobulin (IVIg), intravenous anti-D, danazol, vinca alkaloids, and other immunosuppressive agents such as azathioprine and cyclophosphamide. Platelet transfusions have been used in emergency situations. Several therapies that have been reported, but that are rarely used in chronic ITP, include cyclosporine A, interferon-alpha (IFN-alpha), plasma exchange, staphylococcal protein A immunoadsorption, combination chemotherapy, dapsone, ascorbic acid, and colchicine. Each of these approaches to treatment of chronic ITP are discussed.