Led by the anti-CD20 antibody rituximab, therapeutic monoclonal antibodies have dramatically altered the treatment of patients with non-Hodgkin's lymphoma. As the understanding of the biology of this novel therapy improves, so does the potential for further progress. There are currently four monoclonal antibodies approved by the Food and Drug Administration for the treatment of B-cell malignancies and dozens more are in various stages of development. The indications for the currently available antibodies, both labeled and unlabeled, are being expanded to include first-line treatment, maintenance strategies, and combinations with chemotherapy. Newer agents are being engineered to target novel antigens, and to interact more specifically with the host immune system. These promising therapeutics face a significant challenge in evaluation and integration in the post-rituximab world.