Adenosine receptors are widely distributed in the body and modulate numerous physiological processes. Four receptor subtypes (termed A1, A2A, A2B and A3) have been identified based on their pharmacological profile and cloning. Activation of the A1 adenosine receptors produces a number of effects including a reduction in heart rate and atrial contractility, the attenuation of the stimulatory actions of catecholamines on the heart as well as a reduction of lipolysis in adipose tissue. As a result, A1AR agonists have been targeted as anti-arrhythmic and cardioprotective agents. This review discusses the synthesis, structure-activity relationships and therapeutic potential of A1AR agonists.