G protein-coupled receptors are present on every excitable and regulatable cell in the body and represent important potential sites for drug action. This group of molecules already represents the most common target for currently approved drugs. With recent advances in our understanding of detailed molecular structure, mechanisms of activation, unique molecular associations, and cellular and biochemical mechanisms of regulation of these receptors, development and refinement of receptor-active drugs should benefit substantially. In this report, key past accomplishments and possible future directions for this field of research are reviewed.