The profound hypotensive, sedative, antispasmodic, and vasodilatory actions of adenosine were first recognized over 5 decades ago. During the intervening years the number of biological roles proposed for adenosine and for precursor adenine nucleotides have increased considerably. Extracellular adenosine receptors and adenine nucleotide receptors have been identified. The adenosine receptors appear linked in many cells to adenylate cyclase, while nucleotide receptors probably control ion fluxes. A variety of adenosine analogues and ATP analogues have been introduced in recent years for the study of these receptor functions. Alkylxanthines, such as caffeine and theophylline, are the best known antagonists of adenosine receptors, and some extremely potent xanthine antagonists have been developed recently. However, there do not appear to be any satisfactory specific ATP-receptor antagonists at the present time. The present article will attempt to overview possible physiological roles for adenosine, pathways involved in formation and inactivation of adenosine, the nature of adenosine receptors, profiles of agonists and antagonists, the development of radioactive ligands for adenosine receptors, and strategies for the investigation and exploitation of adenosine functions with agents and tools that specifically affect this complex of reactions and actions.