Epinephrine is the primary drug administered during cardiopulmonary resuscitation (CPR) to reverse cardiac arrest. Epinephrine increases arterial blood pressure and coronary perfusion during CPR via alpha-1-adrenoceptor agonist effects. However, the dose, timing and indications for epinephrine use are based on limited animal data. Recent studies question whether epinephrine provides any overall benefit for patients. A randomized controlled trial indicates that epinephrine for out-of-hospital cardiac arrest increases return of pulses, but does not significantly alter longer-term survival. Very large, well-controlled, observational studies suggest that, despite increases in return of pulses, epinephrine reduces long-term survival and functional recovery after CPR. Detrimental effects were greatest in patients found in ventricular fibrillation. Laboratory data suggest that harmful epinephrine-induced reductions in microvascular blood flow during and after CPR may offset the beneficial epinephrine-induced increase in arterial blood pressure during CPR. The available clinical data confirm that epinephrine administration during CPR can increase short-term survival (return of pulses), but point towards either no benefit or even harm of this drug for more patient-centred outcomes (long-term survival or functional recovery). Prospective trials are needed to determine the correct dose, timing and patients for epinephrine in cardiac arrest.