Cardiomyocytes and vascular cells readily form, transport, and metabolize the endogenous adenine nucleoside adenosine and act to regulate both interstitial and plasma adenosine concentrations. Cardiovascular cells also have membrane adenosine receptors. Cell and tissue distributions, signal transduction pathways, and pharmacology of each of the four subtypes of adenosine receptors are subjects of intense investigation. The A1-adenosine receptors mediate the negative dromotropic, chronotropic, inotropic, and the anti-beta-adrenergic actions of adenosine. Activation of A(2A)- and perhaps A(2B)-adenosine receptors causes vasodilation. Evidence of novel actions mediated by A(2B)- and A3-adenosine receptors is accumulating. Adenosine is cardioprotective during episodes of cardiac hypoxia/ischemia; several potential mechanisms may be involved. Pharmacologic tools are currently available for laboratory investigation of the actions of adenosine, and the development of adenosine receptor subtype-selective agonists and antagonists for therapeutic purposes is beginning.