OBJECTIVE Radioimmunotherapy has emerged as one of the most promising treatment options for hematologic malignancies. This review will present the latest information on radioimmunotherapy for treatment of hematologic malignancies in various clinical settings and assess its long-term safety profile. RESULTS Recent data suggest that radioimmunotherapy with 131I-tositumomab or 90Y-ibritumomab tiuxetan not only induces high response rates but also results in durable remissions in patients with relapsed or refractory indolent non-Hodgkin's lymphomas. Even more notable response rates have been observed when radioimmunotherapy is used as front-line treatment in patients with indolent non-Hodgkin's lymphomas. The use of radioimmunotherapy has been evaluated in the treatment of aggressive lymphomas with promising results, but it remains investigational. Standard doses of radioimmunotherapy given as a conditioning regimen for hematopoietic stem-cell transplant or myeloablative doses of radioimmunotherapy given in conjunction with stem-cell support have yielded encouraging outcomes with durable remissions and a low incidence of treatment-related mortality. CONCLUSIONS The safety and efficacy of radioimmunotherapy has been demonstrated for patients with B-cell lymphomas and other hematologic malignancies in various clinical settings. A number of randomized phase III clinical trials are currently underway to further define radioimmunotherapy's role in the treatment of lymphomas.