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Radioisotope generator systems have traditionally played a central role in nuclear medicine in providing radioisotopes for both research and clinical applications. A resurgence of interest in generator development has been stimulated by advances in antibody technology, instrumentation development, and positron emission tomography (PET). Complementary advances in the development of new chelating agents and radiolabeling techniques for attachment of radioisotopes to various tissue-specific agents have given further impetus to generator research. Widespread interest in the use of antibodies for the radioimmunodetection and therapy of cancer requires readily available sources of radioisotopes with the optimal properties. In this paper, the development of several tungsten-188/rhenium-188 prototype generators which provide rhenium-188 for radioimmunotherapy (RAIT) is discussed. We have recently demonstrated that carrier-free iridium-194 can be obtained from the activated carbon system from decay of reactor-produced osmium-194 for potential RAIT applications. Instrumentation advances such as the new generation of high-count-rate (“fast”) gamma camera systems for first-pass technology require the availability of generator-produced ultra short-lived radioisotopes for radionuclide angiography (RNA). The activated carbon generator is an efficient system to obtain ultra short-lived iridium-191m from osmium-191 for RNA. In addition, the growing number of PET centers has stimulated research in generators which provide positron-emitting radioisotopes. Copper-62, obtained from the zinc-62 generator, is currently used for PET evaluation of organ perfusion. The availability of the parent radioisotopes, the fabrication and use of these generators, and the practical factors for use of these systems in the radiopharmacy are discussed.