Therapeutic advances in the treatment of patients with multiple myeloma continue to be made with the use of novel, nontraditional cytotoxic agents. Recently, these agents, such as thalidomide, lenalidomide, and bortezomib, are being shown in large, randomized clinical trials to be useful options for front-line or salvage therapy. Additionally, research into the molecular pathways of myeloma cell growth and survival has led to the identification of potential therapeutic targets. Finally, advancements in stem cell transplantation continue to emerge. It will be important to provide practicing hematologists/oncologists with a clinically focused overview of these new therapeutic options, which have the potential to impact the current standards of care.