The diagnosis of multiple myeloma (MM) is often difficult; most patients present with asymptomatic gammopathy. The only findings that confirm a diagnosis of MM are an elevation in the M-component or extension of the lytic bone lesions that are the hallmark of the disease. Tests that delineate plasma cell biology, such as plasma cell proliferation rate, are helpful; magnetic resonance imaging can disclose bone marrow lesions leading to subsequent osteolytic disease. After the diagnosis of MM has been established and prognostic factors identified, the appropriate therapy can be determined. Melphalan and prednisone are no longer considered to be the "gold standard" of therapy. In fact, this approach is suitable for less than half of patients with myeloma. This article presents guidelines for standard treatment options and examines the efficacy of new high-dose chemotherapy approaches.