Insulin resistance is an increasingly common metabolic abnormality characterized by an impaired physiological response to insulin. The constellation of insulin resistance and several other metabolic and vascular disorders is known as the insulin resistance syndrome. The characteristic features of the insulin resistance syndrome include central obesity, hypertension, dyslipidemia, glucose intolerance and specific abnormalities of both endothelial cell and vascular function. Although insulin resistance can arise in response to aging, obesity and inactivity, there is a clear genetic component. Insulin resistance is not generally attributable to a single genetic defect. Indeed, it is very likely to be a polygenic disorder in most individuals. A genetic predisposition is suggested to be the demonstration of increased insulin resistance in first-degree relatives of patients with diabetes and by a high incidence of insulin resistance in specific populations. Epidemiological data have demonstrated a strong association between a clustering of specific factors and the risk of cardiovascular disease. The diagnosis of the insulin resistance syndrome remains a significant clinical challenge. At present, clinicians are faced with establishing a clinical diagnosis despite varying definitions of the disorder and controversy regarding how many components presage clinical events. A proposed approach to the management of patients with the insulin resistance syndrome is discussed. © 2003 Lippincott Williams & Wilkins.