More women die every year from cardiovascular disease than men from any other cause. Several fundamental variations have been reported in the mechanisms underlying coronary artery disease, which suggest that its genetic basis varies by gender. Such differences are not limited to gonadal hormones and can be seen in the physiology of atherosclerosis, including plaque components, endothelial function and hemostasis. It is possible to speculate that genetic factors are different in men and women and probably involve biological pathways that have not yet been identified. To date, studies performed by means of the candidate gene approach have identified several genetic variants associated with coronary artery disease in women. However, these scientific data have not been translated into clinical practice. It has recently become possible to search for common gene variants that affect the susceptibility to myocardial infarction on the basis of our knowledge of common single nucleotide polymorphisms and haplotypes across the human genome using genome-wide genotyping technologies. Currently more than 20 gene regions have been associated with ischemic heart disease using this approach. However, so far we do not know several genetic variants differently associated with risk of ischemic heart disease in men and women. A challenge for the near future will therefore be to identify genetic variants that maximally differentiate males from females, and also to identify possible relationships between genes and environment and genes and hormones in both sexes.