Heart failure (HF) is a serious condition representing the end-stage of myriad of cardiovascular diseases. With high prevalence, HF is one of the major focuses in global prevention and management of chronic cardiovascular diseases. Significant progress has been made in pharmacotherapy of HF in past decades, but chronic HF remains to be associated with substantial morbidity and mortality. The recent approval by the US FDA of LCZ696, the first of a new class of drugs with dual angiotensin receptor blocker(ARB) and neprylisin(NEP) inhibition mechanisms, for the treatment of heart failure with reduced left ventricular ejection fraction(HFrEF), represents a major breakthrough in the development of novel pharmacotherapy for HF. In the landmark PARADIGM HF trial, LCZ696 demonstrated significantly improved morbidity and mortality over enalapril, a standard of care in HFrEF. In this review, we discussed the pharmacology, efficacy and clinical application of this new drug.