A door-to-balloon time of less than 90 minutes is the gold standard for reperfusion therapy to treat acute myocardial infarction (MI). Because 30-day mortality remains ∼ 10%, new methods must be cultivated to limit myocardial injury. Therapeutic hypothermia has long been experimentally used to attenuate myocardial necrosis during MI with promising results, but the treatment has yet to gain popularity among most clinicians. Hypothermia, in the basic science setting, has been achieved using many techniques. In our review, we examine past and current methods of inducing hypothermia, benefits and setbacks of such methods, current and future clinical trials, and potential mechanisms.