Neprilysin is a neutral endopeptidase with broad substrate specificity. Among others, it cleaves natriuretic peptides which have a significant role in the pathomechanism of heart failure. This work is a review of literature on neprilysin inhibitors, their mechanism of action, current use, and indications. Emphasis is placed on the use of neprilysin inhibitors in the treatment of heart failure. It reflects the importance and proven efficacy of neprilysin inhibitors in heart failure with reduced ejection fraction. Heart failure is briefly explained, and the different types of heart failure are compared. Sacubitril/valsartan is a neprilysin inhibitor combined with an angiotensin II receptor blocker which has been shown to decrease cardiovascular mortality and hospitalizations, amongst other positive outcomes in patients with HFrEF in the PARADIGM-HF trial. The PARADIGM-HF trial is detailed in this work, followed by a review of the optimal dose titration of sacubitril/valsartan in patients with HFrEF. Use of sacubitril/valsartan is examined in patients with heart failure with preserved ejection fraction in whom regrettably, sacubitril/valsartan had not been shown to be superior to current medical therapy in the large clinical trial. Individuals with characteristics not adequately represented in the PARADIGM-HF trial such as patients with acutely decompensated heart failure and patients with NYHA class IV HFrEF are also discussed. Use of sacubitril/valsartan in patients who develop heart failure after myocardial infarction is currently being examined in ongoing clinical trials and is only briefly mentioned. Clinical trials which made the use of echocardiography are reviewed to show the positive effects of sacubitril/valsartan on cardiac remodeling and left ventricular function. Use of sacubitril/valsartan in clinical setting is touched, as clinicians are currently reluctant to add sacubitril/valsartan to their armamentarium.The cost effectiveness of sacubitril/valsartan for patients with HFrEF is reviewed. There is not enough evidence on the effectivity of sacubitril/valsartan for its use in the treatment of chronic kidney disease in patients who do not have heart failure, despite its positive effects on the kidney in patients with HFrEF. The data on the treatment of hypertension with the use of sacubitril/valsartan in the literature is lacking, but previous clinical trials have shown omapatrilat (neprilysin inhibitor combined with an ACE inhibitor) to lower blood pressure more effectively compared to enalapril alone. There is some data in the literature to suggest that neprilysin may play a role in sleep regulation and two clinical trials are currently planned (although not yet underway) to evaluate this.