A direct, continuous, and independent relation between blood pressure and the incidence of various cardiovascular events, such as stroke and myocardial infarction, is now well accepted. The increase in risk can be attributed to structural and functional changes in target organs. Central to many of these pathophysiologic processes is the renin-angiotensin system (RAS), specifically, angiotensin II. Binding of angiotensin II to angiotensin II type-1 (AT(1)) receptors produces acute vasoconstriction, leading to an increase in blood pressure. AT(1) receptor activation also contributes independently to chronic disease pathology by promoting vascular growth and proliferation, and endothelial dysfunction. These negative consequences of angiotensin II are partly counteracted by angiotensin II type-2 (AT(2)) receptor stimulation, which has favorable effects on tissue growth and repair processes. Thus, the use of selective AT(1) receptor antagonists in the treatment of hypertension has a 2-fold rationale: (1) selective AT(1) receptor blockade targets the final common pathway for all major detrimental cardiovascular actions of angiotensin II, and (2) circulating angiotensin II levels (which increase during AT(1) receptor antagonist treatment) will be free to act only at unopposed AT(2) receptors, potentially providing additional end-organ protection. Angiotensin-converting enzyme (ACE) inhibitors interrupt the RAS by preventing the conversion of angiotensin I to angiotensin II. They also increase plasma levels of bradykinin, which possesses vasodilatory and tissue-protective properties. The combination of an AT(1) receptor antagonist with an ACE inhibitor represents an appealing therapeutic strategy, because it should produce more complete blockade of the RAS, while preserving the beneficial effects mediated by AT(2) receptor stimulation and increased bradykinin levels.