Discuss the literature and describe strategies to overcome barriers of inpatient initiation of sacubitril/valsartan in patients with heart failure with reduced ejection fraction (HFrEF). A PubMed, EMBASE, and Google Scholar literature search (January 2014 to June 2020) limited to English language articles was conducted with the following terms: , , , , , , , , and . Included articles described inpatient initiation of sacubitril/valsartan or described its impact on BNP, NT-proBNP, diuretic dosing, or cost of care. A total of 20 studies were identified based on included search terms. Sacubitril/valsartan should be considered for hemodynamically stable patients with HFrEF (New York Heart Association class II or III), potassium <5.2 mmol/L, without a history of angioedema, and after a 36-hour washout from angiotensin-converting enzyme (ACE) inhibitor or aliskiren, if applicable. An appropriate dose can be determined based on the patient's previous ACE inhibitor or angiotensin receptor blocker dose and/or blood pressure along with patient-specific factors. To overcome barriers of use, the following are recommended: NT-proBNP or BNP with establishment of a new baseline 1 month after initiation may be used for prognosis or diagnosis; careful monitoring of diuretic requirements; utilization of multiple strategies to overcome cost barriers; and use of interdisciplinary care.