The renin-angiotensin-aldosterone system (RAAS) maintains hemodynamic homeostasis through a hormonal cascade: juxtaglomerular cells release renin in response to decreased renal perfusion, sympathetic activation, or decreased sodium delivery to the macula densa. Renin cleaves angiotensinogen to angiotensin I, which is converted by ACE to angiotensin II — a potent vasoconstrictor that also stimulates aldosterone secretion from the adrenal cortex. In heart failure, chronic RAAS activation becomes maladaptive: sustained angiotensin II causes arteriolar vasoconstriction (increased afterload), sodium and water retention (increased preload), myocardial fibrosis, ventricular remodeling, and sympathetic nervous system activation. Aldosterone promotes sodium retention, potassium excretion, myocardial fibrosis, and endothelial dysfunction. This neurohormonal activation creates a vicious cycle: reduced cardiac output activates RAAS, which increases cardiac workload, further reducing output. The clinical rationale for ACEi/ARB/ARNI therapy in heart failure is interruption of this pathological cascade. Sacubitril/valsartan (ARNI) provides dual benefit: neprilysin inhibition augments natriuretic peptides while ARB blocks angiotensin II. Mineralocorticoid receptor antagonists (spironolactone, eplerenone) block aldosterone-mediated fibrosis and fluid retention. Understanding RAAS pathophysiology is essential for the NP to rationally prescribe guideline-directed medical therapy for HFrEF.