The recent approval of 2 radiolabeled antibodies against cluster designation 20-positive lymphoma has led to a resurgence of interest in radioimmunotherapy. As was the case with chemotherapy development, progress has been most marked in the hematologic neoplasms, both in myeloablative and in nonmyeloablative therapeutic strategies. Success in the radioimmunotherapy of solid tumors has lagged because of the immunogenicity of murine proteins and the relatively slow clearance of humanized intact immunoglobulins. Genetic engineering has enabled the development of a variety of antigen-binding constructs of various sizes and immunobiologic characteristics. Developments in radiochemistry as well as production of an increasing number of radionuclides with therapeutic potential or optimal imaging characteristics have spurred tailored therapeutic strategies that include dosimetry and considerations of tumor burden. Such progress has generated pivotal studies that will establish the radiobiologic paradigms for successful radioimmunotherapy of solid tumors. This review will describe seminal studies that have paved the way to an understanding of radioimmunotherapy in solid tumors. Finally, the authors' views of the future of this promising cancer therapy will be presented.