Non-insulin-dependent diabetes mellitus (NIDDM) is one of the most prevalent chronic conditions worldwide. Despite an important role of genetic factors, NIDDM can be viewed as a largely preventable disease. In this article, the current epidemiologic evidence on potentially modifiable determinants of NIDDM is reviewed, including obesity, body fat distribution, physical activity, and dietary factors. Cigarette smoking, parity, and exogenous hormone use are also addressed. Achievable reductions in the risk of NIDDM by favorably altering the modifiable determinants of NIDDM were estimated to be 50%-75% for obesity and 30%-50% for physical activity. Inconsistent results have been observed between specific dietary factors, including saturated fat, sugar, and fiber intake. Data are currently insufficient to provide a reliable estimate of the influence of diet in the prevention of NIDDM. No randomized clinical trial data are available to prove conclusively the benefits of favorable modifications of body weight, body fat distribution, physical activity, and diet on the risk of NIDDM. An extension of research activities to include randomized trials of primary prevention strategies, as well as further observational, clinical, and laboratory research, is needed and strongly recommended.