In this presentation an effort has been made to review the impact of resistance to insulin-mediated glucose uptake and/or hyperinsulinaemia on various metabolic end-points and clinical syndromes. Insulin resistance is present in the great majority of patients with states of glucose intolerance, but frank decompensation of glucose homoeostasis does not occur if individuals can maintain a state of compensatory hyperinsulinaemia. Although compensatory hyperinsulinaemia may prevent the development of NIDDM in insulin-resistant individuals, there is substantial evidence that insulin resistance and/or hyperinsulinaemia is associated with higher plasma concentrations of triglyceride, uric acid and plasminogen activator inhibitor 1 and with lower HDL cholesterol concentrations. Obesity, decreased physical activity and possibly cigarette smoking accentuate the degree of insulin resistance and its manifestations, and a genetic basis is also involved. Resistance to insulin-mediated glucose uptake and/or hyperinsulinaemia have been shown to be associated with high blood pressure, microvascular angina and CHD. Thus, resistance to insulin-mediated glucose uptake is a common phenomenon, which makes a major contribution to the aetiology and clinical course of common and serious diseases. Based on the above considerations, it is difficult to over-emphasize the health-related implication of a defect in insulin-mediated glucose uptake.