A cumulative incidence of diabetic nephropathy of 25% to 40% has been documented after duration of diabetes of at least 25 years in both type 1 and type 2 diabetic patients. Diabetic nephropathy has become the leading cause (25%-44%) of end-stage renal failure in Europe, the United States, and Japan. Until the early 1980s, no renoprotective treatment was available for use in diabetic nephropathy. Death occurred on average 5 to 7 years after the onset of persistent proteinuria. The two main treatment strategies for prevention of diabetic nephropathy are improved glycemic control and blood pressure lowering, particularly using drugs blocking the renin-angiotensin system. Megatrials and meta-analyses have clearly demonstrated the beneficial effect of both the above-mentioned treatment modalities. Secondary prevention, that is, treatment modalities applied to diabetic patients at high risk for developing diabetic nephropathy (eg, those with microalbuminuria) has been documented, applying angiotensin converting enzyme inhibitors and angiotensin II receptor blockade. The renoprotective effects of these drugs are independent of their beneficial reduction in blood pressure.