Autophagy is a maintenance process for recycling long-lived proteins and cytoplasmic organelles. The level of this process is enhanced during ischemia/reperfusion (I/R) injury. Autophagy can trigger survival signaling in myocardial ischemia, whereas defective autophagy during reperfusion is detrimental. Autophagy can be regulated through multiple signaling pathways in I/R, including Beclin‑1/class III phosphatidylinositol‑3 kinase (PI‑3K), adenosine monophosphate activated protein kinase/mammalian target of rapamycin (mTOR), and PI‑3K/protein kinase B/mTOR pathways, which consequently lead to different functions. Thus, autophagy has both protective and detrimental functions, which are determined by different signaling pathways and conditions. Targeting the activation of autophagy can be a promising new therapeutic strategy for treating cardiovascular disease.