Early observations of cardiogenic shock as a systemic clinical syndrome were first described in 1942. Today, cardiogenic shock remains the leading cause of death among patients hospitalized for myocardial infarction (MI). Mortality rates in post-MI cardiogenic shock approach 50% despite rapid revascularization, optimal medical care, and use of mechanical support. New therapeutic strategies with global systemic effects may offer advances in treatment and outcome in post-MI cardiogenic shock. Therapeutic hypothermia for post-MI cardiogenic shock has multiple potentially beneficial physiologic effects, including the potential to improve post-ischemic cardiac function and hemodynamics, decrease myocardial damage, and reduce end-organ injury from prolonged hypoperfusion. Available data in animal models of post-MI cardiogenic shock and ischemia/reperfusion injury and small case series of human patients with cardiogenic shock suggest its promise as a potential therapeutic strategy for cardiogenic shock in the post-MI setting. We hypothesize that systemic therapeutic hypothermia could decrease morbidity and mortality in post-MI patients with cardiogenic shock and warrants study a new treatment that could be widely available at hospitals worldwide.