Despite advances in chemotherapy, radiotherapy and combined modality treatment, a significant proportion of non-Hodgkin's lymphomas remain incurable. The disease usually responds well to chemotherapy or radiation, but relapses are observed within months to a few years, with frequent failure of subsequent therapies. High-dose chemotherapy with or without radiation and autologous or allogeneic hematopoietic stem cell transplantation provide higher cure rates and longer remissions in certain patients with aggressive lymphomas. However, the higher treatment-related morbidity and mortality of high-dose chemotherapy has driven a search for new and more tumor-specific treatment modalities, such as immunotherapy. Tumor antigens expressed by B-cell lymphomas, such as the "idiotype antigen", are seen as unique and specific target molecules for direct lymphoma immunotherapy. This review will delineate advances, problems and prospects for approaches to anti-B cell lymphoma immunotherapy where pre-clinical studies and proof of principle have been directly translated to patient care.