Inherent in the application of advances in biomedical science to nuclear medicine is the concept of molecular targeting: the in vivo concentration of labeled tracer by a gene, its transcribed DNA, or its protein product. This mechanism of localization has been and is being exploited for both nuclear imaging and radioisotopic therapy. Agents, such as antisense molecules, aptamers, antibodies, and antibody fragments, can be aimed at molecular targets. Tumor and nerve cell receptors provide such targets. So do certain cellular physiologic activities, including metabolism, hypoxia, proliferation, apoptosis, angiogenesis, response to infection, and multiple drug resistance. In this article we review the principles of molecular targeting based on radioisotopic methods and provide examples from the literature. We discuss applications to imaging and therapy and point out the hurdles that must be overcome in bringing molecular targeting to clinical reality.