Insulin resistance has a genetic background and its phenotypic expression is triggered by fat diet, lack of physical activity and obesity. It provokes a stress on B cells, tends to increase blood glucose levels, is intimately associated with the metabolic syndrome and represents a major cardiovascular risk factor. Insulin resistance may be favourably influenced by simple life-style changes. If necessary, drugs may be prescribed, such as metformin, the first choice antidiabetic oral agent in overweight individuals, or thiazolidinediones (glitazones), new insulin sensitizers with promising effects. New molecules are currently developed, especially PPAR alpha/gamma or pan-agonists. Targeting insulin resistance has several objectives: reducing hyperglycaemia in type 2 diabetic patients, protecting B cells in order to prevent type 2 diabetes in at risk individuals and limiting the progressive metabolic deterioration in diabetic patients, finally, and perhaps most importantly, ameliorating the global cardiovascular prognosis.