In the past 36 months, new developments have occurred both in the understanding of the biology of Waldenström macroglobulinemia (WM) and in therapeutic options for WM. Here, we review the classification, clinical features, and diagnostic criteria of the disease. WM is a B-cell neoplasm characterized by lymphoplasmacytic infiltration of the bone marrow and a monoclonal immunoglobulin M (IgM) protein. The symptoms of WM are attributable to the extent of tumor infiltration and to elevated IgM levels. The most common symptom is fatigue attributable to anemia. The prognostic factors predictive of survival include the patient's age, beta(2)-microglobulin level, monoclonal protein level, hemoglobin concentration, and platelet count. Therapy is postponed for asymptomatic patients, and progressive anemia is the most common indication for initiation of treatment. The main therapeutic options include alkylating agents, nucleoside analogues, and rituximab. Studies involving combination chemotherapy are ongoing, and preliminary results are encouraging. No specific agent or regimen has been shown to be superior to another for treatment of WM. Novel agents such as bortezomib, perifosine, atacicept, oblimersen sodium, and tositumomab show promise as rational targeted therapy for WM.