The management of multiple myeloma has benefited substantially from the introduction of three new drugs, namely, the proteasome inhibitor bortezomib and the immunomodulators thalidomide and lenalidomide. These drugs were initially shown to improve the outcome of advanced myeloma and were subsequently found to transform the treatment of patients with previously untreated myeloma. Melphalan and prednisone combined with thalidomide or bortezomib is the new treatment of reference for patients who are elderly or ineligible for intensification. The introduction of these new drugs into induction regimens, intensified conditioning regimens, and posttransplantation regimens may improve overall survival among young patients by increasing the rate and quality of the treatment responses. Although myeloma remains incurable, prolonged survival is now a reasonable objective.