Family history represents the contributions and interactions of unique genomic and ecologic factors that affect the metabolic profile and life course of a family and its members. It is well known that a family history of coronary heart disease (CHD) is a significant predictor of an individual's risk for CHD even after adjusting for an individual's own established risk factors, such as hypertension, smoking, and abnormal lipoprotein levels. The explanation for the observed familial disease aggregation is not well understood except for the general knowledge that genetic and environmental factors predisposing to CHD also aggregate in families. Given the multifactorial nature of an individual's risk, it can be argued that an individual's familial risk of disease may, in fact, be a better indicator of the many complex interactions among predisposing genetic and environmental factors than can be captured by an individual's own risk factors. Issues of how to assess, quantitate, and apply family history information in clinical settings still need to be resolved. Some clinical risk indicators, such as the National Cholesterol Education Program III guidelines, take into account family history, while others, such as the Framingham Risk Score, do not. Moreover, several family-centered intervention studies have demonstrated the particular advantages of focusing on families rather than just individuals. Although there has been tremendous progress in primary prevention of CHD over the last 20 years, substantial advancements may still be achieved by focusing on the family as its own unit of inference and as a specific target for disease prevention.