Long-lasting epidemiological studies showed that prevention of coronary artery disease (CAD) is highly feasible with the management of several conditions called "risk factors", such as hypertension, cholesterol, smoking, etc. Nevertheless, risk stratification for primary prevention using a statistical combination of risk factors is suboptimal, as conventional risk factors are age-dependent, so that their treatment would be too late to be effective. Genetic risk stratification, built on the genetic variants linked to CAD, has the advantage of being embedded in DNA and then it is independent of age. The rapid advancement of DNA analysis techniques has made it possible to identify many variants and to produce easily a statistical combination of them to obtain a polygenic risk score (PRS). Prospective clinical trials based on risk stratification for CAD using the PRS have shown that statin therapy is associated with a higher reduction in cardiac events in the high genetic risk group compared with the low genetic risk group. A wide clinical use of the PRS, however, is presently not possible, basically due to the lack of a standard in production and validation of the PRS, but genetic risk stratification has the potential to revolutionize primary prevention.