Multiple myeloma is an incurable plasma cell malignancy that accounts for 10% of all hematologic cancers. For decades the mainstay of therapy has been the use of melphalan and prednisone; with this regimen, the median survival is approximately 3 years. Recently, important advances were made that have substantially altered the manner in which patients with myeloma are treated. Newly diagnosed patients with good performance status are now treated with autologous stem cell transplantation, resulting in improved survival. Because of the increasing use of transplantation as initial therapy, several therapeutic issues have emerged: the role of tandem transplantation, early vs delayed transplantation, and the role of allogeneic transplantation. The pronounced activity of thalidomide in patients with refractory myeloma represents another important advance. This has prompted the study of several novel agents in the treatment of myeloma, at least 2 of which appear promising. Supportive care measures also have improved, including the use of bisphosphonates to prevent osteolytic lesions. The purpose of this review is to summarize recent advances and provide an evidence-based approach to the treatment of multiple myeloma.