Non-Hodgkin's lymphomas (NHL) are a diverse group of malignancies that result, in addition to their treatments, in significant morbidity and mortality in the population. The identification of more effective and better tolerated treatments is of vital importance. Immunotherapy using monoclonal antibodies directed against the CD20 protein has had a profound impact on the management of patients with B-cell NHL. Additional antigen targets are being aggressively investigated. The targeting of lymphoma cells with monoclonal antibodies offers a treatment with a potentially noncross-resistant mechanism of action and a more favorable toxicity profile compared to chemotherapy. Epratuzumab (humanized LL2) is a humanized immunoglobulin G1 monoclonal antibody directed against the CD22 protein in which expression is restricted to mature B cells. Because of important differences in the characteristics of CD22 compared to CD20, epratuzumab may become an important component of future therapies for NHL.