Adenosine's diverse physiological functions are mediated by four subtypes of receptors (A(1), A(2A), A(2B) and A(3)). The A(1) adenosine receptor pharmacology and therapeutic application of ligands for this receptor are the subjects of this review. A(1) receptors are present on the surface of cells in organs throughout the body. Actions mediated by A(1) receptors include slowing of heart rate and AV nodal conduction, reduction of atrial contractility, attenuation of the stimulatory actions of catecholamines on beta-adrenergic receptors, reduction of lipolysis in adipose tissue, reduction of urine formation, and inhibition of neuronal activity. Although adenosine analogs with high efficacy, affinity, and selectivity for the A(1) receptor are available, the ubiquitous distribution and wide range of physiological actions mediated by A(1) receptors are obstacles to development of therapeutic agents that activate these receptors. However, it may be possible to exploit the high A(1) "receptor reserve" for some actions of adenosine by use of weak (partial) agonists to target these actions while avoiding others for which receptor reserve is low. The presence of high receptor reserves for the anti-arrhythmic and anti-lipolytic actions of adenosine suggests that partial A(1) agonists could be used as anti-arrhythmic and anti-lipolytic agents. In addition, allosteric enhancers of the binding of adenosine to A(1) receptors could be used therapeutically to potentiate desirable effects of endogenous adenosine. Antagonists of the A(1) receptor can increase urine formation, and because they do not decrease renal blood flow, are particularly useful to maintain glomerular filtration in patients having edema secondary to reduced cardiac function.