An exciting new era has dawned for the prevention and management of coronary artery disease (CAD) utilizing genetic risk variants. The recent identification of over 60 susceptibility loci for CAD confirms not only the importance of established risk factors, but also the existence of many novel causal pathways that are expected to improve our understanding of the genetic basis of CAD and facilitate the development of new therapeutic agents over time. Concurrently, Mendelian randomization studies have provided intriguing insights on the causal relationship between CAD-related traits, and highlight the potential benefits of long-term modifications of risk factors. Last, genetic risk scores of CAD may serve not only as prognostic, but also as predictive markers, and carry the potential to considerably improve the delivery of established prevention strategies. This review will summarize the evolution and discovery of genetic risk variants for CAD and their current and future clinical applications.