Radioimmunotherapy (RIT) is among the newest modalities for treating the diverse neoplasms known as non-Hodgkin lymphomas (NHLs). The first RIT agent approved by the US FDA was yttrium-90 (90Y) ibritumomab tiuxetan in February 2002. This radioimmunoconjugate consists of the monoclonal IgG1 antibody ibritumomab (the murine parent of rituximab) bound to the chelator tiuxetan and linked by a stable thiourea covalent bond to the β-emitting radionuclide90Y. RIT with90Y ibritumomab tiuxetan is completed in 7–9 days on an outpatient basis, with only minimal (universal) precautions required. The dosing of90Y ibritumomab tiuxetan is based on patient weight and platelet count, after normal biodistribution with indium-111 ibritumomab tiuxetan has been confirmed. Treatment with90Y ibritumomab tiuxetan has produced high response rates and long-term benefits in patients with relapsed or refractory follicular and low-grade NHL, including those in whom rituximab therapy has failed. Its toxicity is primarily hematologic, with the hematologic nadirs generally occurring at 7–9 weeks after treatment. Severe infections are uncommon, with infrequent need for supportive measures such as administration of growth factors and transfusions of blood components. There is little nonhematologic toxicity with RIT and it is generally related to infusion-associated reactions. Clinical trials are investigating ways of increasing the efficacy of RIT. In particular, using RIT earlier in the course of treatment of NHL appears to be a promising approach and has been shown to produce better results than when it is used later. Ongoing research is needed to maximize the efficacy of RIT and minimize adverse events, with the goal of developing a multimodality approach that combines RIT with other biologic agents and possibly chemotherapy as frontline treatment to improve the outcomes in patients with NHL.