C.D. de Langen hypothesized already in 1916 that overnutrition by a cholesterol rich diet is associated with hypercholesterolaemia and the occurrence of atherosclerotic complications such as coronary heart disease. It took till the nineteen fifties before the associations between diet, serum cholesterol and coronary heart disease were systematically investigated. Keys started the Seven Countries Study because he was as De Langen interested in the question whether differences in the occurrence of coronary heart disease between populations could be explained by differences in serum cholesterol and diet. The results of the Seven Countries Study showed that serum cholesterol was strongly related to coronary heart disease mortality both at the population and at the individual level. The strength of the association (relative risks) between serum cholesterol and coronary heart disease mortality was similar in different cultures. However, the absolute risks differed substantially. At a serum cholesterol level of 5.2 mmol/l the 25-year coronary heart disease mortality rate was 5 times higher in Northern Europe compared with Mediterranean Southern Europe. At the population level differences in coronary heart disease mortality rates could almost completely be explained by differences in saturated fat (an important determinant of serum cholesterol), flavonoids (strong antioxidants) and cigarette smoking (producer of pro-oxidants). It can be concluded that the relations between diet, serum cholesterol and coronary heart disease are more complex than originally thought. Not only dietary cholesterol but also different fatty acids and antioxidants play a role in the genesis of atherosclerosis.