As the global burden of type 2 diabetes increases, medical science races to comprehensively understand its molecular aetiology. We suggest that the apparent struggle to seek a pharmacological or molecular victory to the diabetes epidemic is a flawed strategy given that evolution has already provided us with the best medicine. Recent molecular evidence highlights the interaction between muscle fatty acid kinetics in dictating whole body insulin action. Insights from an evolutionary perspective suggest that the ability of the body to evoke insulin resistance and store energy as fat within muscle cells is a normal physiological response to aid our survival during food or carbohydrate scarcity, but this ‘hunter–gatherer physiology’ predisposes to diabetes in a modern environment characterized by ample food availability and muscle inactivity. We contend that the true value of physical activity in the prevention and treatment of insulin resistance has been missed by the medical community because scientific investigation has been constructed upon physical activity recommendations that were never intended for this purpose. These recommendations provide a level of metabolic stress insufficient to be compatible with the expectations of our genes. Copyright © 2005 John Wiley & Sons, Ltd.