Chronic lymphocytic leukemia (CLL) is the most common adult leukemia but is currently incurable by conventional therapeutic interventions. Rituximab has proven efficacy and tolerability in non-Hodgkin's lymphoma, achieving response rates of 73% and 48% in previously untreated or relapsed/refractory indolent non-Hodgkin's lymphoma, respectively. However, the standard dose and schedule (375 mg/m(2) once-weekly for 4 weeks) may not be optimal for patients with previously treated small lymphocytic lymphoma, the lymphomatous equivalent of CLL. Nevertheless, good response rates have been achieved in untreated CLL and small lymphocytic lymphoma using the standard dose and schedule and also using higher or more frequent dosing, indicating that rituximab is an active agent in this setting. More recently, the combination of rituximab and fludarabine or fludarabine-containing regimens has yielded overall response rates of 95%, with complete response rates up to 66% in previously untreated CLL. These response rates are among the highest achieved by any regimen in CLL. These studies indicate that immunochemotherapy with rituximab may offer improved outcomes for patients with CLL. Semin Oncol 30 (suppl 2):34-39.