Myocardial infarction (MI) is the leading cause of death from coronary heart disease and requires immediate reperfusion therapy with thrombolysis, primary percutaneous coronary intervention, or coronary artery bypass grafting. However, myocardial reperfusion therapy is often accompanied by cardiac ischemia/reperfusion (I/R) injury, which leads to myocardial injury with detrimental consequences. The causes of I/R injury are unclear, but are multifactorial, including free radicals, reactive oxygen species, calcium overload, mitochondria dysfunction, inflammation, and neutrophil-mediated vascular injury. Mild hypothermia has been introduced as one of the potential inhibitors of myocardial I/R injury. Although animal studies have demonstrated that mild hypothermia significantly reduces or delays I/R myocardium damage, human trials have not shown clinical benefits in acute MI (AMI). In addition, the practice of hypothermia treatment is increasing in various fields such as surgical anesthesia and intensive care units. Adequate sedation for anesthetic procedures and protection from body shivering has become essential during therapeutic hypothermia. Therefore, anesthesiologists should be aware of the effects of therapeutic hypothermia on the metabolism of anesthetic drugs. In this paper, we review the existing data on the use of therapeutic hypothermia for AMI in animal models and human clinical trials to better understand the discrepancy between perceived benefits in preclinical animal models and the absence thereof in clinical trials thus far.