Diabetic nephropathy is the leading cause of chronic renal failure (CRF) in Europe. About fifty percent of diabetic subjects develop microalbuminuria, which progresses towards established diabetic nephropathy in one third of patients. The treatment of type 2 diabetes in a patient with CRF is a challenge for the general practitioner, because of the accumulation of drugs and/or specific metabolites. Sulfonylureas are associated with an increased risk of hypoglycaemia. Biguanides may exceptionally cause life-threatening lactic acidosis. Glitazones have an interesting profile since they decrease microalbuminuria and blood pressure. However, their safety is not well defined in the context of CRF In the case of severe CRF, only insulin and repaglinide can be recommended.