Diabetes mellitus is the leading underlying cause of end-stage renal disease in the USA. To develop preventive strategies aimed at combatting diabetic end-stage renal disease, three steps are required: first, the delineation of the natural history of diabetic nephropathy; second, the identification of modifiable risk factors for the development and progression of diabetic nephropathy; and third, the demonstration that manipulation of these factors does indeed reduce risk. A review of the literature regarding the epidemiology and prevention of diabetic renal disease in humans published during the past year revealed a wealth of data which may guide preventive efforts. Prospective cohort studies confirmed that microalbuminuria is a strong predictor of nephropathy and that blood pressure is an important modifiable risk factor for the progression of diabetic renal disease. In addition, observational studies identified several novel factors which might also increase risk. Randomized controlled trials provided convincing evidence that strict glycemic control reduces the risk of progression to diabetic nephropathy by 50%. Data from trials also demonstrated that angiotensin-converting enzyme inhibitors slow the progression of renal disease beyond their effect on blood pressure alone. Future research should further evaluate novel modifiable risk factors, define optimal treatment strategies for the use of angiotensin-converting enzyme inhibitors and antihypertensive agents, and develop methods to translate these findings into practice for the general population.