Hypothermia is an established form of treatment employed following cardiac arrest to limit cerebral injury. The question addressed in this review is whether it is possible to use hypothermia to protect the heart during ischemia resulting from ST-elevation myocardial infarction (STEMI). Mild hypothermia (32°C-35°C) may be of benefit as an adjunctive treatment for STEMI by reducing the extent of the infarct and the effects of the four components of ischemia reperfusion injury: myocardial stunning, microvascular obstruction, reperfusion arrhythmia, and lethal reperfusion injury. To reduce cerebral injury after cardiac arrest, hypothermia can be initiated after reperfusion, and should be maintained for 24-48 hours. However, evidence suggests that to protect the heart in cases of STEMI, hypothermia should be initiated as early as possible after the onset of ischemia, at least before reperfusion. Clinical and experimental results indicate that it is of paramount importance to achieve a body temperature below 35°C before reperfusion to reduce the size of the infarct in the treatment of STEMI patients, and that treatment need only be continued for a relatively short period after reperfusion. Hypothermia has wide-ranging effects on most of the mechanisms involved in ischemia and reperfusion injury, which may explain the potent, highly reproducible cardioprotective effects seen in a large number of studies in different species. Subjecting conscious patients with STEMI to hypothermia is safe, feasible, and well tolerated, but antishivering strategies must be employed. Clinical studies are ongoing to evaluate hypothermia as an adjunctive treatment for myocardial infarction. This review discusses the experimental basis for using mild hypothermia to provide cardioprotection, methods of inducing hypothermia, the timing and duration of treatment, and ways in which the knowledge gained can be translated into clinical treatment.