In recent years, there have been major advances in the treatment of multiple myeloma. Among previously untreated patients, different combinations of dexamethasone, lenalidomide, thalidomide, and bortezomib have produced overall response rates of 80%-90% with complete response rates of 10%-32%, and remissions are often achieved after only 2 cycles of initiating systemic therapy. Subsequent intensification with high-dose chemotherapy supported by autologous stem cell transplantation has enabled younger patients to achieve partial and complete responses with evidence of prolonged survival. Tandem autologous stem cell transplantation and reduced-intensity allogeneic stem cell transplantation are under investigation in attempts to improve outcomes. For patients unable to pursue consolidation therapy with stem cell transplantation, remissions obtained with induction therapy can often be extended with the use of maintenance systemic therapy. Despite available therapies, relapse of disease is inevitable for nearly all patients, and treatment strategies with novel agents and novel combinations of established agents are under study.