Our understanding of how insulin regulates carbohydrate, lipid and protein metabolism is relatively sophisticated. Defective insulin action or insulin resistance is one of the earliest defects found in individuals destined to acquire one of many metabolic diseases. However, our understanding of the underlying mechanisms that lead to insulin resistance remains unclear. Many factors including mitochondrial defects, reactive oxygen species and accumulation of toxic lipids in metabolic tissues have been implicated but as to how they cooperate to drive insulin resistance is not known and the major detrimental consequences of insulin resistance that compromise long term health is also debated. Here I will describe new data linking some of the upstream components thus laying the foundation for the description of an “insulin resistance pathway”. I shall describe how a major consequence of insulin resistance is hyperinsulinemia and provide new evidence from our studies in genetically diverse mice as to how fasting insulin levels combined with other metabolic traits can be used to map long term metabolic health providing novel avenues for the discovery of new health targets.