Not all patients who fulfill the minimal criteria for diagnosis of multiple myeloma should be treated. If doubt exists about beginning therapy, one should wait and re-evaluate the patient in 2 or 3 months. There is no evidence that early treatment of multiple myeloma is advantageous. All patients should be considered possible candidates for an autologous stem cell transplantation. If they are deemed to be eligible, they should be treated for 3 to 4 months with therapy that does not damage the hematopoietic stem cells. Currently, most physicians use thalidomide plus dexamethasone or dexamethasone alone for induction. Vincristine, doxorubicin (Adriamycin), and dexamethasone (VAD) have been used in the past. Autologous stem cell transplantation prolongs disease-free survival and overall survival. The treatment-related mortality rate is 1% to 2%. Melphalan, 200 mg/m2, is the most widely used preparative regimen. Although allogeneic transplantation is attractive, the mortality rate (about 20%) is too high to recommend conventional allogeneic transplantation. Non-myeloablative transplantation is currently under investigation. If the patient is not a candidate for autologous stem cell transplantation, therapy with melphalan and prednisone is a good choice. Patients with relapsed or refractory disease may be treated with dexamethasone, thalidomide and dexamethasone, bortezomib (Velcade, PS-341), or lenalidomide (Revlimid, not yet approved by the Food and Drug Administration).