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Identification of prognostic factors associated with MMM have not impacted the treatment of the disease, which continues to be palliative with the exception of allogeneic stem cell transplantation (SCT) for potential long\u2010term disease\u2010free survival in selected patients. Additional insights into the pathophysiology of MMM have resulted in the use of novel therapeutic strategies in the treatment of this disease. The rationale for the investigation of these agents in MMM and the status of clinical trials with various modalities such as angiogenesis inhibitors (e.g., thalidomide), tyrosine kinase inhibitors (e.g., imatinib mesylate), farnesyl transferase inhibitors (e.g., R115777), and other agents are reviewed, in addition to the potential roles of autologous and allogeneic SCT. 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