The development of effective B cell-directed monoclonal antibody therapies has dramatically altered the management of patients with B-cell non-Hodgkin's lymphoma. Anti-CD20 murine and chimeric antibodies have been characterized by manageable toxicity profiles and appear to have mechanisms which may be distinct from and complementary to those of chemotherapy. There is considerable rationale for treatment strategies which target other B-cell antigens, including CD22. This molecule is commonly expressed in non-Hodgkin's lymphoma and may mediate important functions in B-cell biology. Laboratory and initial clinical studies suggest that epratuzumab, a humanized anti-CD22 monoclonal antibody, may have antilymphoma activity in both unlabeled and radiolabeled forms. Efforts are underway to establish the utility of epratuzumab as a treatment for B-cell malignancies, through single agent and combination regimens, to define the optimal settings for its clinical application.