The common forms of cardiovascular disease (CVD) have a complex etiology, involving multiple genetic influences and important environmental interactions. Because of this complexity, it has proved difficult to apply the positional cloning approaches that have revolutionized understanding of Mendelian (single-gene) disorders; and the understanding of the genetics of CVD and its underlying cause, atherosclerosis, remains poor. This review, organized into 10 broad questions, summarizes the understanding of the genetics of common, complex forms of CVD. Implications for DNA-based diagnosis, pharmacogenetics, and risk assessment are also discussed.