Non-insulin-dependent diabetes is a worldwide disease. In the United States nearly 10 million persons are affected and the prevalence is increasing. Considerable advances in the understanding of the pathogenesis and determinants of non-insulin-dependent diabetes have occurred in recent years. Genetic and environmental determinants are associated with the development of diabetes, but the mode of inheritance of the genetic determinants is unknown. Obesity, particularly if it is centrally distributed and of long duration, is the most prominent environmental risk factor for non-insulin-dependent diabetes. Although it has long been suspected as an etiological factor, evidence that physical activity is a predictor of the disease is now emerging. The adoption of a western lifestyle and improvements in socioeconomic conditions are at least partially responsible for the very high rates of diabetes among several ethnic and racial groups, although the specific components of these changes that contribute to development of non-insulin-dependent diabetes are still uncertain. Other factors that worsen insulin resistance are likewise predictive of the development of disease. An understanding of the risk factors for non-insulin-dependent diabetes may lead to more specific intervention, and possibly to prevention of this disease.