There is evidence that coronary artery disease (CAD), hypertension, diabetes mellitus (DM) and hyperlipidemia develop due to interaction of genetic and environmental factors during transition from poverty to affluence. Rapid transition in diet and lifestyle factors may influence heritability of the variant phenotypes that are dependent on the nutrient environment for their expression. We are beginning to recognize the interaction of specific nutrients with the genetic code possessed by all nucleated cells. In the next millennium, the physician may be able to make nutrient intake recommendations not on physical characteristics but on the basis of the individual's phenotypic expression for health while suppressing his phenotypic expression for disease. We have demonstrated an increased susceptibility to CAD, diabetes, central obesity, hyperinsulinemia and lipoprotein(a) excess in Indians in younger age groups indicating a genetic predisposition to these problems due to interaction of gene and environment. Lipoprotein(a) is a genetic risk factor for CAD, diabetes and stroke and it is higher in South Indians than North Indians. Antioxidant vitamins, coenzyme Q10 and n-3 fatty acids may have a beneficial influence whereas linoleic acid, saturated fat and sugars may have adverse effects on phenotypic expression. There is significant evidence that genes are involved in determining enzymes, receptors, cofactors, structural components involved in regulation of blood pressure, the metabolism of lipids, lipoproteins and inflammatory and coagulation factors that are involved in determining an individual's risk. Majority of these genes are polymorphic. While some genes respond to nutritional modulation, others may not indicate any response.