Autophagy is known as a conserved mechanism in order to preserve cell survival under various stress conditions via maintaining cellular homeostasis. Although autophagy is active in the heart at baseline and plays a critical role in cell survival, inappropriate activation of autophagy following ischemia/reperfusion (I/R) injury leads to cell death.The distinct functions of autophagy in myocardial I/R injury condition have been examined in numerous studies, however, contradicting results have been achieved in this field. These studies have documented that autophagy acts as a double-edged sword in myocardial I/R injury. Clarifying the exact role of autophagy in determining the health or death of cardiomyocytes under I/R injury is very helpful to achieve better cardioprotection in prospective clinical studies. Thus, autophagy may be an interesting target for the treatment or prevention of myocardial I/R injury. But before considering this matter, it is necessary to address the gaps in our knowledge about the complex role of autophagy in myocardial I/R injury.In this review, by providing updated data about the role of autophagy in the heart during ischemia and reperfusion, we tried to provide more insights in this context and encourage scientists to pay special attention towards manipulating autophagy as an intriguing and powerful approach in cardioprotection.