Autologous stem cell transplantation (ASCT) is currently considered the standard of care for younger patients with newly diagnosed multiple myeloma based on 3 randomized trials that have shown it is superior to conventional chemotherapy. However, the introduction of novel agents like thalidomide, bortezomib, or lenalidomide may improve the results of standard-dose therapy. For instance, in combination, melphalan/prednisone/thalidomide yields complete response rates comparable with those achieved with ASCT. Different strategies have been proposed to improve the results of ASCT. A randomized trial has shown that tandem ASCT is superior to single ASCT in terms of event-free survival (EFS) and overall survival. Four other randomized trials have produced results in favor of tandem ASCT. However, the benefit remains marginal and patients with poor initial characteristics still have poor outcomes. Further intensification has been tested with encouraging results in patients with high b2-microglobulin levels and chromosome 13 deletion. "Total Therapy II" with intensified induction and post-ASCT chemotherapy also appears to improve outcomes. Another possibility is the use of novel agents in combination with ASCT as part of induction therapy or as maintenance therapy after ASCT. Preliminary results of a French Intergroup study show a significant prolongation of EFS in patients receiving maintenance therapy with thalidomide. Results achieved with allogeneic stem cell transplantation remain disappointing. Although initial results of ASCT followed by reduced-intensity allogeneic stem cell transplantation were promising, with more follow-up, relapses and chronic graft-versus-host disease have limited the enthusiasm. Allogeneic stem cell transplantation should be proposed only in the context of a clinical trial.