Diabetic nephropathy is the major cause of illness and premature death in people with diabetes, largely through accompanying cardiovascular disease and end-stage renal failure. Diabetic patients are several times as prone to kidney disease as nondiabetic people and the accumulative risk of diabetic nephropathy in insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM) is about 30%-50% after 25 years of disease. Diabetic nephropathy is a progressive disease that takes several years to develop, ending in chronic renal insufficiency. Proteinuria heralds the onset of diabetic nephropathy, and the worsening of proteinuria parallels the progression of renal disease. The main risk factors for the frequency, severity, and progression of diabetic nephropathy are the degree of hyperglycemia and associated metabolic disturbances, hypertension, protein overload, cigarette smoking, as well as the duration of diabetes. Interventional strategies for primary, secondary, and tertiary prevention of diabetic nephropathy therefore include meticulous glycemic control, appropriate treatment of associated lipid abnormalities, rigorous control of the blood pressure, reduction in dietary protein intake, in particular animal protein, and of fat intake, and stopping cigarette smoking. Randomized clinical trials indicate that antihypertensive therapy is beneficial in preventing and slowing down the progression of diabetic nephropathy. There is now increasing evidence that angiotensin-converting enzyme inhibitors and certain calcium antagonists produce a more beneficial effect on diabetic nephropathy in terms of reducing proteinuria and slowing the progression to diabetic renal failure. These drugs are attributed nephroprotective capacity beyond their blood pressure lowering capacity and initial clinical trials with combinations have revealed even additive protective effects on end organs.