Radioimmunotherapy (RIT) with Yttrium-90 (90Y) ibritumomab tiuxetan (Zevalin) combines the tumor targeting attributes of a monoclonal antibody against the CD20 antigen and the pure beta-radiation of 90Y. High efficacy and a favorable safety profile have been demonstrated in Phase II and III clinical trials enrolling patients with CD20+ B-cell non-Hodgkin lymphoma (B-NHL). On the basis of these results, 90Y-ibritumomab tiuxetan was approved in the United States for the treatment of patients with follicular lymphoma (FL) or transformed B-NHL. In the European Union its use was restricted to FL, refractory to or relapsed after rituximab. There are a number of important clinical trials currently evaluating 90Y-ibritumomab tiuxetan in other subtypes of lymphoma such as diffuse large-cell and mantle-cell lymphoma, as consolidation therapy or as part of myeloablative regimens. In light of the constantly increasing clinical experience with RIT, clinicians face the challenge of how to best integrate this promising new treatment option into existing established treatment algorithms. By incorporating the most recent data in this rapidly developing field, this review article focuses on current recommendations for the use of 90Y-ibritumomab tiuxetan in patients with malignant lymphoma, outlines future perspectives, and provides practical recommendations for patient management.