The European Society of Cardiology (ESC), Canadian Cardiovascular Society, and the American College of Cardiology Heart Failure (HF) guidelines all currently recommend the use of Angiotensin Converting Enzyme (ACE) inhibitors or Angiotensin Receptor Blockers (ARBs) and Beta Blockers (BB) in the treatment of HF with a reduced ejection fraction (HFrEF). Newer medications targeting combining an ARB with a neprilysin inhibitor (ARNI) sacubitril/valsartan have shown benefits in mortality and can be used in place of an ACE inhibitor or an ARB. Additionally, dapagliflozin, a medication targeting the sodium-glucose cotransporter 2 (SGLT2) can be used in addition to current therapies.This review provides a comprehensive analysis of the evidence around the new pharmacotherapies for HFrEF, specifically, sacubitril/valsartan and dapagliflozin. A comprehensive review of the literature using keywords such as heart failure with reduced ejection fraction, angiotensin receptor, neprilysin inhibitor, and sodium glucose transporter was conducted within the National Centre for Biotechnology Information (NCBI) and Google Scholar databases. The reference sections of articles were also examined to find additional articles.Sacubitril/valsartan and dapagliflozin both show marked benefits on mortality in HFrEF patients. More research needs to be conducted on the mechanisms of action on disease modification.