Waldenström's macroglobulinemia is a rare B cell malignancy. All prognostic studies have identified the adverse prognostic effect of advanced age and low hemoglobin level for survival, whereas the prognostic value of a high level of monoclonal component remains controversial. Response to treatment is probably a favorable prognostic factor for overall survival. Conventional treatment is based on alkylating agents, and especially chlorambucil. Purine analogues, used initially for salvage treatment, are increasingly employed as front-line therapy. Purine analogues have not been compared with alkylating agents as first-line therapy in randomized trials, and it is unclear whether purine analogues extend survival. An anti-CD20 monoclonal antibody has given a response rate in about 30% of patients. Autologous and allogeneic stem cell transplantation may be considered for patients with refractory or relapsing disease.