Several studies have demonstrated that a prolonged over-activation of neurohormonal mechanisms contributes to drive structural and functional abnormalities of the cardiovascular system and leads to poor prognosis in patients with congestive heart failure (CHF). In particular, activation of the renin-angiotensin-aldosterone system (RAAS) leads to increased levels of angiotensin II and plasma aldosterone, and promote development of arterial vasoconstriction and remodeling, sodium retention, oxidative process, and cardiac fibrosis. Angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers and beta-blockers may modulate this excessive over-activity and improve survival in those patients. However, high circulating and tissue levels of angiotensin II and aldosterone may persist and contribute to further progression of CHF. Many aspects of the pathophysiological role of the RAAS in CHF are still debated, and a more thorough comprehension of this fundamental system is needed. This article reviews the current knowledge on the biochemical and functional organization of the RAAS, its pathophysiological role in CHF, and the potential therapeutic implications.