The incidence of obesity, noninsulin-dependent diabetes mellitus (NIDDM), hypertension, and coronary artery disease has increased in the developed world. At the same time, major changes in the type and amount of fatty acid intake have occurred over the past 40-50 years, reflected in increases in saturated fat (from both animal sources and hydrogenated vegetable sources), trans fatty acids, vegetable oils rich in linoleic acid, and an overall decrease in long chain polyunsaturated fatty acids (arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid--C20-C22). Recent findings that C20-C22 in muscle membrane phospholipids are inversely related to insulin resistance, whereas linoleic acid is positively related to insulin resistance, suggest that diet may influence the development of insulin resistance in obesity, insulin-dependent diabetes mellitus (IDDM), hypertension, and coronary artery disease (including asymptomatic atherosclerosis and microvascular angina). These conditions are known to have genetic determinants and have a common abnormality in smooth muscle response and insulin resistance. It is proposed that the current diet influences the expression of insulin resistance in those who are genetically predisposed. Therefore, clinical investigations are needed to evaluate if lowering or preventing insulin resistance through diet by increasing arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid, while lowering linoleic acid and decreasing trans fatty acids from the diet, will modify or prevent the development of these diseases.