The use of radionuclides for medical and for a multitude of other basic research applications has continued to grow at a very rapid pace. Procedures, based on their use as radiotracers for nuclear medicine imaging and for radiotherapy of cancer and other pathology, have become firmly established as important clinical modalities. It is estimated that on an annual basis in the United States alone, radionuclides are used medically in over 13 million imaging procedures, in over 100 million laboratory tests, and in an ever increasing number (> 100,000) for therapeutic administrations. One out of every four hospital patients undergoes a procedure that involves the use of radionuclides. Diagnostic imaging methods using planar/single-photon emission computed tomography and positron-emission tomography (PET) imaging, as well as the measurement of in vivo organ function, physiology, or biochemistry, have become indispensable tools in patient workup and management. More than 80% of all imaging studies (mostly anatomic) currently use technetium-99m (99mTc), because it has turned out to be the ideal isotope from various considerations. However, over the past few years, nuclear medicine has experienced a slow but steady evolution towards functional studies, quantitative PET imaging, and novel therapeutic approaches. New radionuclides are required for these applications, and their development has attracted considerable interest. This article reviews the current status and future prospects for the development of many new potential isotopes. Practical issues, such as the feasibility of large-scale production and wide-spread availability in a continuous reliable fashion, are addressed. To date, the data are not sufficient to answer the question as to whether any of these radionuclides (or their applications, for that matter) will eventually assume as broad-based a role as that of 99mTc. Nonetheless, there are a number of promising radionuclides that could assume an important place in the future practice of nuclear medicine.