Abstract Myeloma is a malignancy of plasma cells that are terminally differentiated B-lymphocytes. The clinical spectrum varies from the incidental discovery of a pathologically raised monoclonal immunoglobulin on routine electrophoresis in asymptomatic patients to widespread skeletal involvement with incapacitating bone pain. Symptoms may result from a solitary tumor mass, described as an extramedullary plasmacytoma, in virtually any part of the body. Metabolic abnormalities commonly include hypercalcemia, elevated plasma urate levels, or the development of amyloidosis, all of which may disturb renal function. High paraprotein levels cause hyperviscosity, resulting in generalized debility and varying degrees of disturbed mental function. The natural history is determined by the mass of the tumor coupled with its unique biologic features. Median survival of unselected patients, without effective treatment but once symptoms are evident, is approximately 7 months; this period can be significantly prolonged with appropriate therapy. As a first step, urgent medical management is often necessary, centering on rehydration, correction of hyperviscosity, and reversal of metabolic defects, each of which may improve renal function. Over the longer term, specific antitumor drugs have extended median survival to approximately 30 months, and most regimens include a combination of melphalan and prednisone, with or without other cytotoxic drugs. Alternative forms of treatment include sequential hemibody irradiation, recombinant alpha interferon, and in suitably selected patients, high-dose chemoradiotherapy followed by bone marrow transplantation. The latter approaches offer promising management options and are currently the subject of evaluation in controlled clinical trials.