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Cardiovascular disease (CVD) is a designation for multiple clinical phenotypes that result from the interaction of genetic variants, lifestyle choices, and environmental exposures. This article points to the utility of assessing a person's family history of CVD, which is the sum of genetic factors, environment and common lifestyle influences, which may be shared among family members and provides information useful for estimating risk for CVD. It also presents several approaches utilized in attempts to identify variants in genes that are involved in the etiology of CVD. Specifically, examples of the candidate gene approach to identify genetic risk factors for coronary heart disease from our own research are presented. The utilization of genetic profiling to predict an individual's long-term prognosis, to target preventive strategies, and to select the most efficacious drug for treatment are discussed, as well as, the need to consider newer approaches to understanding complex diseases.