New approaches to the definition and treatment of hypertension have increased emphasis on reducing overall cardiovascular risk and on targeting the underlying mechanisms of cardiovascular disease. During the past several decades, renin-angiotensin-aldosterone system (RAAS) activation has emerged as an important factor in the pathophysiology of endothelial dysfunction and cardiovascular disease (CVD). Angiotensin-converting enzyme inhibitors (ACEIs) have well-established efficacy for treating CVD, but their use may be limited by intolerable side effects, such as cough and angioedema. Angiotensin II receptor blockers (ARBs), a different class of RAAS inhibitors, are considered a viable alternative to ACEIs. Clinical trials have further elucidated the role of ARBs in CVD. This article reviews the mechanism of action of ARBs and selected clinical trials of ARBs in CVD.