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The renin-angiotensin-aldosterone system (RAAS) is considered to be the main mediator of the cardiovascular damage associated with high blood pressure. Recent guidelines recognised, both directly and indirectly, the central role of RAAS, reporting the ‘compelling indications’ for the use of drugs that antagonise this system. The results of many large trials with the angiotensin receptor blockers (ARBs) candesartan, losartan, irbesartan and valsartan have been published from the year 2000 to the end of 2003. These trials have been conducted to verify that, beyond blood pressure control, ARBs could offer better organ protection in many different clinical conditions. Despite the favourable premises, some ARB trials not only failed to show superiority, but even equivalence with lower-cost therapies of confirmed efficacy (e.g. captopril 50mg three times daily). On the contrary, other ARB trials (IDNT [Irbesartan Diabetic Nephropathy Trial], IRMA2 [Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria], RENAAL [Reduction of End points in NIDDM with the Angiotensin II Antagonist Losartan], and LIFE [Losartan Intervention for End Point Reduction in Hypertension]) have had such clear-cut outcomes that irbesartan (300mg) and losartan (100mg) are the drugs of choice in type 2 diabetes patients with proteinuria or in hypertensive patients with left ventricular hypertrophy. The key factor for ARBs to succeed in delivering superior organ protection appears to be the high dosages used, dosages uncommonly utilised, with some exceptions, to treat hypertension in clinical practice. The results of the published ARB trials are reviewed, focusing on the dose-efficacy of target-organ protection beyond blood pressure control.