OBJECTIVE To review the available standard treatment regimens for multiple myeloma. METHODS Studies from the literature were summarized, and the efficacy of various chemotherapeutic regimens for induction, maintenance, and relapse therapy was assessed. RESULTS For many years, standard therapy for multiple myeloma has been intermittent cycles of melphalan+prednisone (MP). Although administration is easy and clinical responses are frequently good, treatment failure usually occurs in less than 2 years, and the 5-year survival is low. The combination regimens of vincristine sulfate, 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), melphalan, cyclophosphamide, and prednisone (VBMCP) and two that feature 3-week cycles of melphalan and cyclophosphamide alternating with BCNU and Adriamycin (doxorubicin hydrochloride), either with (VMCP/VBAP) or without (ABCM) vincristine and prednisone, reportedly yield more frequent and durable responses and a higher 5-year survival than MP. Although a meta-analysis of 18 published trials found no overall difference in efficacy between MP and combination chemotherapy, the end point analyzed was only 2-year survival, and the studies were possibly too heterogeneous to afford valid comparisons. Currently, the high response rates, improved duration of disease control, and generally good toxicity profile of VBMCP, ABCM, and VMCP/VBAP make them the preferred primary treatment in patients who can tolerate more intensive therapy than MP. Elderly patients who are bedridden may have difficulty with VBMCP and related regimens and should receive MP instead. Promising results have been obtained with alternating cycles of VBMCP and recombinant interferon-alpha. As maintenance therapy, interferon has delayed relapse, whereas MP has consistently been ineffective. In patients with relapses after unmaintained responses to VBMCP, reinduction therapy with the same regimen can yield a 1-year response. CONCLUSIONS Although the issue is still unresolved, data suggest that combination chemotherapies are superior to MP for treating multiple myeloma.