Heart failure (HF) is a heterogeneous disorder with complex mechanisms. A thorough understanding of its pathophysiological mechanism reveals that neprilysin (NEP) plays an important role in its incidence and development. So inhibiting NEP provides a new direction and target for the treatment of HF. Recently, angiotensin receptor neprilysin inhibitor (ARNI) makes great progress in the management of heart failure with reduced ejection fraction (HFrEF), whereas no clinical trial to date has yet identified an effective therapy for heart failure with preserved ejection fraction (HFpEF). In the 2016 updated HF guidelines of American Heart Association and European Association of Cardiology, ARNI is recommend as a drug for chronic HFrEF. This article reviewed the research advance in HF and NEP.