Radioimmunoconjugates are radioisotope-bound monoclonal antibodies that target radiation specifically to sites of lymphoma involvement. Initial studies of 90Y-ibritumomab tiuxetan in non-Hodgkin's lymphoma (NHL) have suggested benefit in patients with relapsed or refractory indolent disease. However, the routine adoption of this agent is tempered by concerns of associated toxicities and unclear long-term benefit. A comprehensive search for studies on 90Y-ibritumomab tiuxetan use in lymphoma was completed. The aims of this systematic review were to summarize and evaluate the evidence on: (1) the benefits and risks of this novel therapy; (2) predictors for response and toxicity; and (3) the role of dosimetry and imaging studies prior to treatment. A total of twenty trials investigating the use of 90Y-ibritumomab tiuxetan for the treatment of adult patients with NHL were identified. In trials of patients with relapsed or refractory indolent NHL, overall response rates ranged from 67 - 83%. In patients with follicular NHL refractory to the monoclonal antibody, rituximab, response rates remained high (74%). However, in rituximab-naïve patients with relapsed or refractory indolent or transformed NHL, the higher response rate seen with 90Y-ibritumomab tiuxetan therapy compared to rituximab monotherapy has not translated into clear improvements in time-to-progression or survival. 90Y-ibritumomab tiuxetan is an active agent in relapsed and refractory non-Hodgkin's lymphoma that should be considered in select patients.