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. The gene discussed is SLC5A2; the disease is heart failure.