The development of rituximab, an anti-CD20 monoclonal antibody, represents a revolutionary advance in the therapy of hematological malignancies. Rituximab was approved in 1997 by the Food and Drug Administration for the treatment of relapsed or refractory, CD20(+), B-cell, low-grade or follicular non-Hodgkin's lymphoma (NHL). Recent studies have documented activity of rituximab in other CD20-expressing hematological malignancies including mantle cell lymphoma, small lymphocytic lymphoma, aggressive NHL, chronic lymphocytic leukemia, and Waldenstrom's macroglobulinemia. When used in combination with cytotoxic chemotherapy, rituximab achieves response rates of 90%-95% in low-grade follicular and aggressive NHL patients. Currently, rituximab is undergoing intensive investigation in several large phase II and III trials, both as a single agent and in combination with chemotherapy. Clinical research will help define the ultimate role of this agent and its potential impact on survival of patients with B-cell neoplasms. This article describes current clinical trials with rituximab and discusses their significance.