Hyperinsulinaemia is of great importance, being a primary risk factor for cardiovascular disease and non-insulin dependent diabetes (NIDDM). Furthermore, unwanted effects of increased exposure of tissues to insulin are known. Hyperinsulinaemia may, in principle, be caused by primary hypersecretion, or be a secondary consequence of diminished effectiveness of insulin in the periphery. Obesity is the commonest condition characterized by insulin resistance, which is seen most frequently when excess adipose tissue is localized to the abdominal region. Insulin resistance in obesity is found in several tissues, however, with liver and muscle being quantitative the most important. Muscle insulin sensitivity is regulated by genetic factors, hormonal effects, and the influence of free fatty acids, as well as the state of physical activity. There is evidence for the action of each of these factors in obesity. The pathogenetic mechanisms linking hyperinsulinaemia with cardiovascular disease and NIDDM are unknown. Comparisons between development of NIDDM in experimental animal models and in humans in prospective studies however, provide useful hypotheses for further studies.