This article gives an overview of sacubitril/valsartan (Entresto), a first-in-class angiotensin receptor-neprilysin inhibitor comprising valsartan, an angiotensin II receptor blocker and the neprilysin inhibitor sacubitril. The drug has been approved for the treatment of symptomatic (NYHA class (II-IV) chronic heart failure and reduced ejection fraction (HF-REF) in adults.