Diabetic nephropathy (DN) is now the commonest cause of end-stage renal failure in the Western world. Recent studies examining the pathogenesis of diabetic complications have focused on the complex interaction between genetic and hemodynamic mechanisms in addition to metabolic factors such as advanced glycation, protein kinase C (PKC) activation, and polyol production. The importance of the various components, particularly with regard to the progression of DN, is currently being explored with the assistance of targeted drug intervention studies.