Until recently, the potential relevance of genetic, biochemical and lifestyle factors to coronary heart disease have been studied in relative isolation from one another. Although this approach has yielded some major insights, it has resulted in a fragmented and incomplete understanding of the relative importance and interplay of nature and nurture in the development of coronary risk. New opportunities for more integrated, powerful and comprehensive approaches have been opened by major developments, including: establishment, collation and maturation of relevant population bioresources; emergence of technologies that enable rapid and accurate assessment of many genetic and biochemical factors, without necessitating assumptions about biological mechanisms; and advances in statistical analytical methods. This chapter provides a critical review of the strengths and limitations of established and emerging epidemiological approaches to the study of the separate and combined effects of genetic, biochemical and lifestyle factors in coronary heart disease.