Targeted immunotherapy utilizing monoclonal antibodies has improved survival in both indolent and aggressive lymphoma significantly. Since malignant lymphomas are also responsive to radiation, the combination of targeted immunotherapy and radiation with radionuclide coupled to monoclonal antibodies is an attractive option to further improve treatment results. Zevalin is a commercially available variation of the murine anti-CD20 antibody ibritumomab coupled to Yttrium 90 via the tiuxetan chelator. The development of this novel drug as well as the results of the pivotal studies and clinical strategies to implement this treatment into the routine practice of lymphoma oncology are presented in this review.