Cardiovascular disease represents a continuum that starts with risk factors such as hypertension and progresses to atherosclerosis, end-organ damage, and ultimately to chronic heart failure (CHF) and premature death. Renin-angiotensin system (RAS) blockade with angiotensin converting enzyme (ACE) inhibitors and/or angiotensin II type 1 receptor blockers (ARBs) has turned out to be beneficial at all stages of this continuum. Several mechanisms govern the progression of structural myocardial damage to end-stage CHF. Chronic neuroendocrine activation fosters left ventricular remodeling and dilatation and leads to clinical symptoms of CHF via forward/backward failure. RAS inhibition is a cornerstone of neuroendocrine blockade in CHF patients, and combined RAS blockade is especially effective in patients presenting with repetitive cardiac decompensations. This review focuses on the therapeutic role of inhibitors of different RAS components in chronic heart failure caused by systolic left ventricular dysfunction.