The application of epidemiology to the study of non-insulin-dependent diabetes mellitus (NIDDM) is providing new insights into many aspects of this major public-health problem, including its natural history, prevalence, incidence, morbidity, and mortality in diverse populations around the globe. The main impetus came from the late Kelly West's book Epidemiology of Diabetes and its Vascular Lesions. These studies are providing direction for research into the possible molecular defect or defects and biochemical mechanism or mechanisms underlying NIDDM and important information on the extrinsic (social, cultural, environmental) risk determinants. Studies have highlighted the importance of regional adipose tissue distribution, particularly upper-body obesity, and physical inactivity in enhancing risk of NIDDM. These findings have important implications for the primary prevention of NIDDM, particularly in populations with increased genetic susceptibility such as Polynesians, Micronesians, American and Asian Indians, Mexican Americans, and Australian aborigines. Hyperinsulinemia and insulin resistance may be present many years before the onset of NIDDM and clearly play an important role in its etiology. There is some evidence to support the contention that hyperinsulinemia and insulin resistance may also play an important causal role in hypertension, dyslipidemia, upper-body obesity, and, through these risk factors, coronary artery disease. Hyperinsulinemia and/or insulin resistance may be a central factor in the etiology of glucose intolerance, hypertension, dyslipidemia, upper-body obesity, and atherosclerosis, which has very important implications for the primary prevention of these disorders. That both weight reduction and exercise reduce insulin resistance and reduce the levels of some of the other risk factors for coronary artery disease provides strong support for an integrated approach to the primary prevention of NIDDM and cardiovascular disease, although it seems paradoxical that prevention is now a possibility, whereas, the molecular and biochemical mechanisms involved in the etiology of these disorders are not fully understood.