Common multigene disorders account for 80% of deaths in the world and all have significant genetic predisposition. Coronary artery disease and myocardial infarction (MI) account for more than 40% of these deaths. The genetic component is due to multiple genes, each contributing only minimally to the phenotype. Linkage analysis, which has been successful in identifying rare disorders that cause MI, is not sensitive for multigene disorders. The recent candidate case-control approach has been equally unsuccessful. Multigene disorders require genome-wide association studies involving genotyping hundreds of thousands of DNA markers in thousands of individuals with replication in independent populations. Platforms with 500,000 and 1 million single nucleotide polymorphisms provide the necessary high-throughput genotyping for genome-wide association. The first confirmed common locus, 9p21, is independent of conventional risk factors. Identifying the 9p21 gene will elucidate novel mechanisms responsible for MI. Comprehensive prevention of MI based on individual genetic variants (personalized medicine) is expected in the next decade.