Multiple Myeloma (MM) is a B cell neoplasia affecting approximately 14,400 new individuals in the United States each year. Although MM remains an incurable disease, encouraging advances have been made in its therapy in the recent past. High dose chemotherapy with autologous stem cell transplantation has been shown in randomized controlled trials to improve survival in MM and is currently considered the first line treatment for all patients except those with advanced age of co-morbidities. For such patients, conventional chemotherapy with melphalan and steroids continue to be the treatment of choice. The use of tandem stem cell transplants and the use of both myeloablative and nonmyeloablative allogeneic stem cell transplantation remains investigational. Thalidomide is a new therapeutic option with promising results; however, it is associated with significant side effects including deep venous thrombosis and peripheral neuropathy. Its use in combination with other chemotherapy agents is still under investigation. Novel promising agents are currently under clinical trials including Proteosome Inhibitors and much more potent thalidomide analogs or immunomodulators. This review summarizes recent developments in the therapy and supportive care of MM and introduces the newer drugs in preclinical and early clinical trials.