Radioimmunotherapy (RIT) is a promising new therapy for the treatment of a variety of malignancies. General principles of RIT are discussed, including important considerations in the selection of monoclonal antibodies (MAb) and radionuclides for RIT. Results of clinical trials using RIT for the treatment of lymphoma, leukemia, and solid tumors are summarized. The results from many of these trials are promising, especially for the treatment of lymphohematopoietic malignancies, in which a variety of MAb, radionuclides, and study designs have resulted in high response rates with a number of durable responses. Encouraging results have also been obtained using RIT to treat some solid tumors, primarily in patients with relatively low tumor burdens. RIT is generally well tolerated, with the primary toxicity being transient reversible myelosuppression in most nonmyeloablative studies. Nonhematologic toxicity, especially at nonmyeloablative doses, has been minimal in most studies. Approaches for increasing the therapeutic index of RIT are reviewed, which may further potentiate the efficacy and decrease the toxicity of RIT.