Lee E. Limbird Department of Pharmacology and Center for Molecular Neuroscience, Vanderbilt University School of Medicine, and Vanderbilt Kennedy Center for Research on Human Development, Nashville, Tennessee 37232 T his review briefly summarizes the development of the receptor concept, the identification of receptors based first on biological response data and subsequently on radioligand binding prop- erties, and the biological and physiological understandings that these approaches have made possible. The development of receptor characterization began with receptors that ultimately were discovered to mediate response by coupling to G-binding proteins, also known as G protein–coupled receptors (GPCRs). Consequently, many if not all of the examples in this overview will describe studies character- izing GPCRs in general, and adrenergic receptors in particular. The purpose of this review, however, is not a detailed chronological account of a huge literature, but rather an overview of the fundamental questions posed and answered by these studies. The Receptor Concept: The Receptor Concept: A Continuing Evolution 326