Abstract: Heart failure (HF) is the final stage of cardiovascular disease and a complex clinical syndrome, which mainly manifested as systolic and diastolic dysfunction of the heart. Although the treatment of HF drugs are constantly updated, the fatality rate of it remains higher. Therefore, exploration of new therapeutic targets of HF is always in progress. Recent researches have shown that AMP-activated protein kinase (AMPK) is involved with the occurrence and development of HF. AMPK can regulate the myocardial metabolism, myocardial fibrosis and oxidative stress during the time of HF. In this review, we will discuss the mechanisms of AMPK in protecting HF and the progression of related drugs.