After the discovery and clinical use of insulin for treatment of diabetes it became clear that some of the biological effect of insulin was dependent on the circumstances under which it was given. Relevant for this review is the notion that physical activity, in addition to its own direct metabolic effects also markedly affects the ability of insulin to stimulate a range of metabolic processes. More specifically, during and for a prolonged period after, exercise elicits effects on processes such as insulin-induced muscle glucose uptake and glucose metabolism which influence systemic glucose homeostasis. These phenomena are probably responsible for the improvement in glucose homeostasis and metabolic control that typically occurs with exercise in people with insulin resistance and probably contributes to the reduced risk for development of type 2 diabetes in individuals who engage in regular exercise. Here we focus on the influence of a single bout of exercise on the action of insulin on processes such as glucose uptake and glucose storage in skeletal muscle.