ABSTRACT Multiple myeloma (MM) is a B cell neoplasm of the bone marrow with a complex array of clinical manifestations including anemia, bone lesions, hypercalcemia, renal dysfunction, and compromised immune function. It accounts for 10%-15% of all hematologic malignancies, and 20% of deaths related to cancers of the blood and bone marrow. The diagnosis of MM is based on the presence of neoplastic plasma cells in the bone marrow or other extramedullary sites, along with evidence of disease-related organ dysfunction. Although the disease remains incurable, significant advances in both basic and translational research have enhanced understanding of disease pathogenesis and guided the development of new and more effective therapies. These agents include the immunomodulatory drugs thalidomide and lenalidomide, the proteasome inhibitor bortezomib, and other therapeutics that are currently being evaluated. This review highlights important historical landmarks in the field of MM, examines the pathogenesis and clinical manifestations of the disease, and outlines principles of both diagnosis and treatment of MM.