The renin-angiotensin system (RAS) represents today one of the most strategic targets of the therapy of cardiovascular diseases. During the last 30 years a number of more or less successful approaches to inhibit the activity of the RAS have been attempted. In particular, the use of ACE-inhibitiors has led to significant improvments in the outcom/treatment of hypertension, congestive heart failure, ischemic heart disease and nephropathies. On the other hand, Ace-inhibitors are not specifically targeted to RAS since they interfere with an enzyme with multiple different substrates. Furthermore, the inhibition of ACE does not prevent the formation of angiotensin II through alternative pathways, and thus the inhibition of RAS is often incomplete, especially under pathologic conditions stimulating RAS. For these reasons, the recent discovery of angiotensin ii receptors antagonists, which selectively inhibit the action of angiotensin II at the level of the AT1 subtype receptor, is particularly attracting. This article reviews the background, the rationale and some of the clinical findings and potential applications with this new class of compounds.