The use of epinephrine during cardiac arrest has been advocated for decades and forms an integral part of the published guidelines. Its efficacy is supported by animal data, but human trial evidence is lacking. This is partly attributable to disparities in trial methodology. Epinephrine's pharmacologic and physiologic effects include an increase in coronary perfusion pressure that is key to successful resuscitation. One possible explanation for the lack of epinephrine's demonstrated efficacy in human trials of out-of-hospital cardiac arrest is the delay in its administration. A potential solution may be intraosseus epinephrine, which can be administered quicker. More importantly, it is the quality of the basic life support, early and uninterrupted chest compressions, early defibrillation and postresuscitation care that will provide the best chance of neurologically intact survival.