Waldenstrom's macroglobulinemia (WM) is a B-cell disorder characterized by bone marrow infiltration with clonal lymphoplasmacytic cells (LPCs), along with an immunoglobulin M monoclonal gammopathy. Recent studies have led to several insights into disease biology as well as the development of an international staging system. Patients with asymptomatic macroglobulinemia should be observed without therapy. Options for frontline therapy include alkylating agents, nucleoside analogs, and rituximab, either as monotherapy or in combination. Although objective responses are common, complete remissions are infrequent. Several novel agents including proteasome inhibitors and thalidomide, as well as high-dose chemotherapy and stem cell transplantation are being incorporated into the therapeutic armamentarium in WM and show promising activity. This report provides an update on recent advances in biology and treatment of this disease.