[en] The development of technetium-99m-labeled small-molecule radiopharmaceuticals directed at specific high-affinity binding sites, as are found in receptors for hormones and neurotransmitters, transport systems, and certain enzymes, is a natural outgrowth from the successful development of technetium radiopharmaceuticals for imaging flow and metabolism. Although many receptor-specific radiopharmaceuticals labeled with PET and other SPECT isotopes already exist, the low cost and widespread availability of technetium-99m would make their ^99mTc-labeled counterparts much more accessible to the medical community. This review has four goals: (a) To survey and analyze critically the results of a flurry of research activity in this area in recent years, which has led to the preparation of a number of novel technetium-labeled radiopharmaceuticals targeted at high-affinity sites, a few of which appear to be very promising; (b) to provide a conceptual analysis of how these agents are being designed; (c) to provide a context in terms of binding and uptake behavior by which these agents should be judged; and (d) to highlight emerging knowledge on the structure of receptors and related high-affinity binding biomolecules and their distribution, which may serve as reference points for understanding the results that have been obtained so far, and may be useful guides for future design