In this review, we discuss what is meant by “foundational” therapy for patients with heart failure and reduced ejection fraction (HFrEF) and the evidence supporting the use of the five agents that comprise this group of drugs i.e., sacubitril/valsartan, a beta‐blocker, an aldosterone or mineralocorticoid receptor antagonist (MRA) and a sodium‐glucose cotransporter 2 (SGLT2) inhibitor. Here, NR3C2 is linked to heart failure.