Multiple myeloma represents the second most common hematologic malignancy, with nearly 15,000 new cases each year in the United States. Although further understanding of the pathogenesis of this B-cell malignancy has been made, the disease remains incurable with a median survival of approximately 3 years. The identification of new genetic events in the malignant cells themselves may lead to new potential therapies. Moreover, recent identification of the new human herpesvirus 8 in the supporting cells of the bone marrow of these patients will likely change approaches to this disease in the laboratory and the clinic. Further development of new high-dose therapy approaches has led to a reduction in treatment-related mortality with an improvement in overall survival. Treatment with the bisphosphonate pamidronate reduces skeletal complications and may also improve overall survival of these patients.