Waldenstrom's macroglobulinemia (WM), a rare B-cell malignancy, is incurable. Conventional treatment consists of alkylating agents (especially chlorambucil), with or without corticosteroids. Purine analogues such as fludarabine are also active. Response rates to first-line therapy range from 38% to 85%. Discrepancies in response rates between different studies could be due to the small patient populations in two studies and to differences in patient characteristics and response criteria. Since 1990, several phase 2 trials of purine analogues have been done with previously treated patients; fludarabine induced responses in about one third of patients who were resistant to previous treatments. Response rates to fludarabine in previously treated patients range from 30% to 50% and are highest among patients who are still sensitive to their primary therapy. The responses last from 32 to 41 months. The principal toxicity of fludarabine is myelosuppression. Trials of fludarabine combination therapy with drugs such as rituximab are ongoing.