Ferroptosis is a novel type of cell death, which is closely modulated by multiple signaling transduction pathways including iron homeostasis pathway, cystine/glutamate transporter (System XC－) pathway and voltage-dependent anion channel (VDAC) pathway. Although there is evidence that ferroptosis contributes to myocardial ischemia/reperfusion injury, many questions remain to be solved, such as which stage ferroptosis mainly appear following myocardial ischemia/reperfusion? Is it a necessary condition for the involvement of iron in ferroptosis? It is of significance for seeking novel drugs to protect the heart against ischemia/reperfusion injury once the mechanisms for ferroptosis are elucidated.