Myocardial infarction is responsible for most cardiovascular mortality as well as the pathogenesis of myocardial damage during and after infarction. Efforts are underway to modulate the development of ischemia– reperfusion (I–R) injury. Recently, the protective effect of isoflurane against myocardial I–R injury emerged as a possibility. Nitric oxide, nitric oxide synthases, factors related to energy metabolism, adenosine triphosphate- sensitive potassium channels, phosphatidylinositol-3-kinase and hypoxia-inducible factor1-alpha have been shown to participate in the mechanisms of cardioprotection elicited by isoflurane against I–R injury. In this review, we focus on the mechanisms of cardioprotection offered by isoflurane against I–R injury.