The initial view of the renin-angiotensin system focused on the role of angiotensin II as a hormone involved in blood pressure control, based on its role in renal salt and water regulation, as well as central nervous system (thirst) and vascular smooth muscle tone. Subsequent data showed a role for angiotensin II in long-term effects on cardiovascular structure, including cardiac hypertrophy and vascular remodeling. Importantly, recent human studies with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers have demonstrated exciting clinical benefits including decreases in incidence of stroke, diabetes, and end-stage renal disease that suggest important new mechanisms of action. In this review, we focus on new roles for the renin-angiotensin system in the endothelium based on the concepts of diverse signals and effects mediated by multiple angiotensin I- and angiotensin II-derived peptides, multiple angiotensin metabolizing enzymes, multiple receptors, and vascular bed-specific intracellular signals.