Enthusiasm for the use of monoclonal antibodies, such as rituximab, has markedly changed the approach to patients with non-Hodgkin lymphomas (NHLs). Nevertheless, more effective therapies are needed. Radioimmunotherapy as a form of targeted radiation therapy may add significantly to our therapeutic options. Yttrium Y 90 ibritumomab tiuxetan, recently approved by the Food and Drug Administration, and iodine I 131 tositumomab have demonstrated a high level of activity in patients whose NHL has failed to respond to chemotherapy and rituximab. Toxicities have primarily included prolonged myelosuppression, with a potential risk of treatment-associated myelodysplastic syndrome and acute myelogenous leukemia. Ongoing clinical trials are attempting to better characterize the role of these promising agents.