The renin-angiotensin system (RAS) is one of the body's most powerful regulators of arterial pressure and body fluid volumes. Although the acute effects of angiotensin II (AngII), the primary active component of the RAS, on arterial pressure are mediated primarily by peripheral vasoconstriction, its chronic BP effects are closely intertwined with volume homeostasis, particularly with intrarenal actions that influence pressure natriuresis. AngII shifts pressure natriuresis toward higher BP primarily by increasing tubular reabsorption rather than decreasing GFR. In fact, activation of the RAS can serve as an important means of preventing decreases in GFR during volume depletion or circulatory depression. However, with prolonged excess AngII formation, particularly in association with hypertension or overperfusion of the kidney, AngII can contribute to glomerular injury and a gradual loss of nephron function through its hemodynamic actions. The multiple effects of AngII to increase tubular reabsorption provide a powerful mechanism to protect against volume depletion and low BP. However, when AngII levels are inappropriately elevated, this necessitates increased arterial pressure to maintain sodium and water balance. Blockade of the RAS has proved to be a powerful therapeutic tool for lowering BP and improving kidney function in disorders such as hypertension, congestive heart failure, and chronic renal disease.