The clinical development of immunotherapy with rituximab (chimeric anti-CD20 monoclonal antibody) has markedly affected the treatment approach for patients with B-cell non-Hodgkin's lymphoma (NHL). Rituximab was initially evaluated in relapsed indolent lymphoma and has substantial activity in this setting both alone and in combination with chemotherapy. Ongoing efforts in indolent NHL are seeking to optimize the dose and schedule of rituximab through "maintenance" strategies exploring chemotherapy-rituximab combinations and the use of other biologic agents or antibodies that may enhance activity when employed together with rituximab. Other studies in indolent NHL suggest that radiolabeled anti-CD20 antibodies (such as I-131 tositumomab and Y-90 ibritumomab tiuxetan) may be useful in relapsed and refractory disease and have potential utility as part of initial treatment as well. In diffuse large B-cell lymphoma, the addition of rituximab to CHOP chemotherapy can improve survival, though benefits are more limited in mantle cell lymphoma. Further studies of unlabeled and radiolabeled immunotherapies are ongoing in order to optimize their use for maximal clinical benefit.