Adenosine 5'-triphosphate (ATP) plays a critical role in intracellular metabolism and energetics. Extracellular ATP is rapidly degraded to adenosine by ectoenzymes. Both ATP and adenosine suppress cardiac pacemakers' automaticity and atrioventricular nodal conduction, albeit via the different mechanism of actions. This historical update summarizes the current knowledge regarding the negative chronotropic and dromotropic actions of ATP and discusses the clinical implications regarding the utility of ATP as a diagnostic and therapeutic agent in the management of neutrally mediated syncope and paroxysmal supra ventricular tachycardia.