Reduction of elevated blood pressure clearly protects against target organ damage, but the different targets do not necessarily benefit to the same degree. There is considerable debate over whether or not there is a drug-specific benefit above and beyond that conferred by blood pressure reduction alone. We performed a Medline search to identify recent randomized clinical trials including 300 or more patients who were followed for at least 2 years. We critically reviewed these papers to find like trials for comparisons. There was too much dissimilarity to perform a meaningful meta-analysis. We found that the literature does not support a definitive conclusion either in favor of or against an overall drug-specific protective effect. However, by grouping like trials, it is possible to support an additional protective effect by angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on reducing the rate of decline in renal function and in reducing proteinuria.