Despite considerable advances in preventative treatment during the last two decades, the increasing burden of cardiovascular (CV) disease constitutes an urgent need for new therapeutic strategies to reduce CV mortality and morbidity in patients at high CV risk. Activation of the renin-angiotensin system (RAS) results in vasoconstrictive, proliferative and pro-inflammatory effects that contribute to the development of atherosclerosis. As a result, the RAS is implicated at all stages of the 'CV continuum' that links risk factors such as hypertension and dyslipidaemia with major CV events, congestive heart failure (CHF) and CV death. The RAS therefore represents a rational and ideal therapeutic target in CV risk reduction strategies. Both angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) have been shown to promote beneficial effects on end-organ damage, such as decreases in arterial stiffness and left ventricular hypertrophy (LVH). Several trials have shown that ACE inhibitors and ARBs reduce CV risk in patients with specific risk factors. Furthermore, the HOPE study and, more recently, the ONTARGET® study have shown that ramipril and telmisartan reduce CV risk in patients with a high CV risk profile across the 'CV continuum'. Telmisartan is the first ARB to demonstrate CV prevention in patients at high CV risk, similar to that of the gold-standard ACE inhibitor, ramipril. This extensive clinical trial evidence suggests that ACE inhibitors or ARBs should be part of the standard treatment for patients at risk of CV events. ARBs may represent a preferred option due to their unsurpassed tolerability.