High-dose melphalan (200 mg/m2) followed by one or more autologous peripheral blood stem cell transplantations is a safe and effective treatment regimen for multiple myeloma. This treatment regimen is as effective as standard therapy for myeloma in older (>65 years) patients and in patients with renal failure. However, advanced age (>50 years), duration of prior standard therapy (> 12 months), and a low CD34 mobilization potential (<20 x 10(6)/kg) are associated with a higher incidence of cytogenetic myelodysplasia. Future efforts directed at curing multiple myeloma should incorporate the best remission induction regimens presently available and should use consolidation/maintenance treatment (eg, idiotype/dendritic cell vaccination and dexamethasone/cyclophosphamide/etoposide/cisplatin combination chemotherapy) to enhance sustained complete remission. Other options to improve the treatment of myeloma include novel adjunctive therapies that target the myeloma cell microenvironment (eg, bisphosphonates, thalidomide, other antiangiogenesis agents) and allogeneic transplantation techniques to induce a graft-versus-myeloma effect.