Coronary artery disease is a complex disease influenced by modifiable risk factors as well as genetic susceptibility. The genetics of coronary artery disease and myocardial infarction have long been enigmatic. Recent advances in molecular genetics and biology, bioinformatics, and statistics have allowed us to study the interaction of exogenous and endogenous factors. Recent genome-wide association studies and their meta-analyses have included thousands of patients and healthy individuals and provided the statistical power to identify genetic variants, each associated with a rather small increase in risk. Thus far, more than 45 risk loci have been identified. Nevertheless, the search for genetics-based improvements in therapy and prevention has just begun. Hitherto unrecognized mechanisms may provide promising drug targets and early interventional strategies. Furthermore, the sum of risk alleles may facilitate risk assessment as they provide complementary information to traditional risk scores.