Diabetic nephropathy is one of the leading causes of end-stage renal failure worldwide, and is associated with high cardiovascular mortality. It is the consequence of the combined effect of environmental and genetic factors. The reduction in incidence with glycemic control demonstrates the important role of metabolic alterations. Blood pressure control, notably with blockers of the renin-angiotensin-aldosterone system, has been shown to slow the progression of renal disease. Current data show that diabetic nephropathy is not just a microvascular complication of diabetes, but that other cell types such as epithelial cells and podocytes are affected at an early stage and contribute to the genesis of renal disease. A more precise understanding of the pathophysiological mechanisms of diabetic nephropathy will enable us to develop targeted therapeutic strategies and prevent kidney damage.