Type 2 diabetes mellitus is now the leading cause of end-stage renal disease in the United States and other developed countries. The pathogenesis of renal failure in type 2 diabetes is complex, but a role of the reninangiotensin system (RAS) has been recognized for more than 15 years. In recent years, this notion has been confirmed by several large-scale clinical trials in patients with type 2 diabetes and renal disease. Blockers of the angiotensin II type 1 receptor (ARB) ameliorate the progression of overt nephropathy, independent from BP. Angiotensin-converting enzyme inhibitors (ACEI) as well as ARB decrease microalbuminuria and delay the progression from microalbuminuria to overt nephropathy. The recently published BENEDICT trial showed that ACEI retarded the development of new-onset microalbuminuria in hypertensive patients with type 2 diabetes, whereas a control antihypertensive drug did not. These trials supported a role of the RAS and marked a considerable step forward in the treatment of the disease. Nevertheless, several questions regarding the role of RAS blockade in type 2 diabetes remain to be answered. Are ARB superior to ACEI, or is a combination of both the most effective treatment? What are the optimal doses of ARB and ACEI? Can RAS blockade at best retard progression, or are these drugs able to reverse the loss of renal function as well? At what stage should RAS blockade be initiated? What is the role of nonhemodynamic mechanisms for the effects of RAS blockade?