Ethyl pyruvate is a simple derivative of the endogenous metabolite, pyruvic acid. Ethyl pyruvate was shown to ameliorate some of the structural and functional changes associated with mesenteric ischemia and reperfusion in rats.Treatment with ethyl pyruvate has been shown to improve survival and ameliorate organ dysfunction in a wide variety of preclinical models of critical illnesses, such as severe sepsis, acute respiratory distress syndrome, burn injury, acute pancreatitis and stroke. Ethyl pyruvate has been shown to improve cardiac function after coronary ischemia and reperfusion. This ester was originally regarded as a way to administer pyruvate, while avoiding some of the problems associated with the instability of pyruvate in aqueous solutions. Increasingly, however, it is becoming apparent that certain pyruvate esters, including ethyl pyruvate, have pharmacological effects, such as suppression of inflammation, which are distinct from those exerted by pyruvate anion. Ethyl pyruvate has been tested in human volunteers and shown to be safe at clinically relevant doses.Ethyl pyruvate is a simple molecule that has been shown to have salutary effects in numerous large and small animal models of critical illness. It remains to be determined whether this ester can be used successfully to treat human diseases.