Although the underlying cause of the metabolic syndrome (MS) is not entirely clear, it is thought that MS results from central obesity and insulin resistance (IR). IR has long been known to be a predictor of type 2 diabetes in many populations, including American Indians, the group with a rising prevalence of obesity and the highest rate of diabetes in the United States. In addition to being a predictor of diabetes, MS has now been shown to be associated with higher risk of cardiovascular disease, independent of diabetes, in American Indians as well as in other ethnic groups. Furthermore, MS may carry a risk beyond that of single risk factors. Identifying MS in American Indians and treating the factors that comprise it may reduce risk of both diabetes and cardiovascular disease in this population.