In recent years, a target blood pressure (BP) of at least 125/75 mmHg has been sought in order to reduce the rate of progression of chronic renal failure (CRF) and cardiovascular mortality. Some antihypertensive agents, such as ACE inhibitors, calcium channel blockers and angiotensin receptor antagonists (and perhaps endothelin converting enzyme inhibitors and endothelin antagonists), may also reduce CRF progression because they block some of the pathogenetic mechanisms involved in renal damage. Although this effect seems to be partially independent of BP reduction, it is still not clear whether these drugs are really superior to other antihypertensive agents when low BP is achieved. However, the possibility that combination treatments with some of these drugs may confer additive or even synergistic renoprotective effects other than BP control is not only fascinating, but also important because multidrug antihypertensive regimens are required anyway to manage BP adequately in the majority of patients with CRF.