The treatment for non-Hodgkin's lymphoma (NHL) has improved over the past 20 years, but the natural history of the disease has not improved with conventional therapeutics. New modalities using targeted therapy based on molecular biology and immunology hold promise for better outcomes with less toxicity. Major radionuclides available (iodine I 131 and yttrium 90) are discussed and clinical trial data with the 90Y-labeled antibody ibritumomab tiuxetan are presented. Long-term toxicity questions are addressed, the use of dosimetry as a means for predicting toxicity is reviewed, and quality-of-life analyses are discussed. Radioimmunotherapy represents a safe and effective treatment modality for patients with NHL.