Over recent years, a target blood pressure of 125/75 mm Hg has been sought in order to reduce the rate of chronic renal disease (CKD) progression and cardiovascular mortality. Some antihypertensive agents, such as angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists and calcium channel blockers also may be capable of reducing CKD progression because they halt some of the pathogenetic mechanisms involved in renal damage. The possibility that combination treatments with ACE inhibitors and calcium-channel blockers may confer additive or even synergistic renoprotective effects other than blood pressure control is not only fascinating, but also particularly important because multidrug antihypertensive regimens are required to obtain adequate blood pressure in the majority of patients with CKD. This combination may provide better blood pressure control, appears to be better tolerated with fewer side effects than either drug alone, and may exert a greater renoprotective effect in patients at risk for renal failure than either an ACE inhibitors or a calcium channel blocker. However, the current available data are too few to confirm this hypothesis. Cardiovascular disease accounts for more than 50% of the deaths of hemodialysis patients. Thus, care must be taken to prevent and treat the cardiovascular risk factors optimally from the early phase of CKD, and for this reason effective antihypertensive therapy is the most important treatment, not only in order to delay CKD progression, but also to reduce the burden of cardiovascular disease. In this perspective combination therapy with ACE inhibitors and calcium channel blockers can give further advantages.