Adenosine is a ubiquitous substance that is released under several physiological and pathological conditions and has cardiovascular effects including cardioinhibition and vasodilation. It has been shown to be an important modulator implicated in several forms of syncope. In patients with chronic low plasma levels of adenosine, a transient release of endogenous adenosine can be sufficient to block conduction in the atrioventricular node and induce prolonged asystole; conversely, when plasma adenosine levels are chronically high, adenosine release is responsible for vasodepression. Distinct purinergic profiles in patients presenting with syncope have recently been correlated with the clinical presentation: “low-adenosine patients,” prone to asystole, may present with idiopathic atrioventricular block, carotid sinus syndrome, or syncope with no or very brief prodromes and normal heart; “high-adenosine patients,” prone to vasodilation, experience vasovagal syncope. This pathophysiological classification may have therapeutic implications.