The scientific development of immunotherapies and radioimmunotherapies of cancer began more than four decades ago. Over time, it has become apparent that the choice of target antigen, immunogenicity of antibodies, length of antibody half-life, ability of antibodies to recruit immune effector functions, decision on conjugation of antibodies to toxins or radionuclides and antibody manufacturing are critical components of successful development of an immunotherapeutic regimen. Anti-idiotype antibodies were some of the first successful monoclonal antibody treatments developed for non-Hodgkins lymphoma. In 1997, the chimeric antibody, Rituximab, was approved by the United States Food and Drug Administration for treatment of patients with relapsed or refractory low-grade or follicular non-Hodgkins lymphoma. In an effort to enhance the efficacy of immunotherapy, toxins and radionuclides have been conjugated to monoclonal antibodies. Ibritumomab, the parent murine antibody of Rituximab, is conjugated to the radioisotope 90Y to create 90Y Ibritumomab tiuxetan, (90Y Zevalin, IDEC-Y2B8). Promising Phase I/II trials have been completed. Phase III experimental trials of 90Y Ibritumomab tiuxetan as treatment for relapsed or refractory NHL are in progress.