In Japan, over the last 40 years, the change in lifestyle, particularly the westernization of the diet, has led to increased frequency of "lifestyle-related disorders" such as, hyperlipidemia, diabetes mellitus, and atherosclerosis. Consequently, the morbidity and mortality due to coronary heart disease have increased, and the prevention of this disorder is now one of the major concerns when considering the quality of life of individuals and the public health policy. Hyperlipidemia, particularly hypercholesterolemia, is one of the major risk factors of atherosclerosis. Therefore, the clarification of the mechanisms of the development of hyperlipidemia is important in the consideration of the prevention and management of atherosclerotic disorders. Genetic and epidemiological studies have provided compelling evidence that genetic factors, environmental influences and the interaction between them all contribute to the development of this complex disorder. Various unexpected mechanisms of the development of hyperlipidemia have been elucidated by analyzing some hereditary disorders. Furthermore, the cloning of the genes involved in the maintenance of cholesterol and/or lipid homeostasis has made it possible to investigate the molecular mechanisms of the development of hyperlipidemia in detail. Elucidation of the genetic and environmental factors and detailed understanding of the molecular pathophysiology of hyperlipidemia are essential in the pursuit of evidence-based preventive medicine and health policy.