Coronary artery disease (CAD) is highly heritable. The technological advances over the past decade have enabled faster and more comprehensive genetic analysis with a simultaneous lowering of costs. This has resulted in a better understanding of the genetic determinants of atherosclerosis and CAD, and thus an increasing interest in and demand for polygenic risk scores (PRSs) to evaluate the genetic susceptibility for developing these diseases. Polygenic risk can be quantified already at birth, long before other risk factors used to predict CAD, and before clinical manifestations of disease. PRSs can identify 10–20 times as many individuals at high risk compared to monogenic mutations, and PRSs for CAD add more predictive information to a baseline model than any other of a number of traditional risk factors. Nevertheless, the introduction into clinical practice of PRSs is not without challenges, and the clinical utility and applications of PRSs are still debated