Not all patients who fulfill the minimal criteria for the diagnosis of multiple myeloma should be treated. If a patient is younger than 70 years, autologous peripheral blood stem cell transplantation should be seriously considered. Major challenges for stem cell transplantation are: 1) the inability to eradicate multiple myeloma from the patient, and 2) removal of myeloma cells and their precursors from the reinfused stem cells. Allogeneic transplantation cannot be recommended at present because of the excessive mortality. Nonmyeloablative approaches are promising. There is no evidence that combinations of alkylating agents are superior to melphalan and prednisone. The use of thalidomide and intermittently administered prednisone for maintenance is being explored. New agents include the immunomodulatory drugs, inhibitors of the ubiquitin proteasone pathway such as PS-341, antiangiogenesis drugs including 2-methoxy-estradiol, and farnesyl transferase inhibitors. Management of skeletal complications, hypercalcemia, anemia, infection, spinal cord compression, and renal insufficiency is discussed.