This review briefly summarizes the development of the receptor concept, the identification of receptors based first on biological response data and subsequently on radioligand binding properties, 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 characterizing 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.