Immunotherapy directed against the CD20 antigen has had a profound impact on the management of patients with B-cell non-Hodgkin's lymphoma (NHL). Antibody-based treatments offer a favorable side effect profile, as well as alternate mechanisms of action that may complement those of cytotoxic modalities. Targeting other antigens, such as CD22, may also result in antilymphoma effects. This B-cell-specific molecule is widely expressed in NHL and mediates important functions in B-cell biology. Preclinical and early clinical data suggest that epratuzumab, a humanized anti-CD22 monoclonal antibody, demonstrates antilymphoma effects in both unlabeled and radiolabeled forms, as well as a favorable safety profile. Ongoing and future studies will further determine the role of epratuzumab among the array of antilymphoma therapies, both as a single agent and in combination with other agents.