Neprilysin (NEP) is a ubiquitous metallopeptidase that can hydrolyze a variety of peptides in the body. Current studies have shown that NEP can affect the progression of heart failure by regulating the natriuretic peptide system, renin-angiotensin-aldosterone system, and kinin-kallikrein system, etc. Because the benefits of angiotensin receptor neprilysin inhibitor has also been confirmed in clinical applications, NEP can be used as a new target for the treatment of heart failure. However, because of the wide application of NEP′s effects, it has aroused widespread concern about its safety in the clinical treatment of heart failure.