In this review, the pathophysiologycal events leading to hyperglycemia in NIDDM patients are discussed, i.e. glucose effectiveness, insulin action (in muscle and liver) and insulin secretion. The natural history of the insulin resistance syndrome is demonstrated and a new staging system is proposed. We conclude that NIDDM is a life-long disease characterized by intraabdominal obesity and macrovascular events several years in advance of hyperglycemia, and that insulin resistance in skeletal muscle plays an important pathophysiological part and also may be used in prediction of the disease.