Multiple myeloma remains an incurable cancer. In recent years, progress in different drug classes has improved outcomes, but management has become more complicated. Areas such as prognostic classification, the increased use of high-dose chemotherapy with autologous stem-cell rescue, and a wider array of ancillary drugs must be integrated into recommendations for a consolidated treatment plan. Estimating prognosis is dependent on both clinical features and a growing list of laboratory tests. Autologous transplantation has been applied to an increasing proportion of patients, at different points in the disease process. Besides the age cut-off issue, there are still significant treatment choices to be made within the transplant technique. Newer drugs, most recently, thalidomide (Thalomid), may offer benefits independent of conventional cytotoxic drugs or steroids. Use of ancillary drugs, such as bisphosphonates, interferon, P-glycoprotein blockers, antibiotics, and growth factors, are also discussed. For the future, immunotherapy in the posttransplant setting appears promising. Ultimately, basic research must identify intracellular targets for the development of specific new-generation drugs.