The Food and Drugs Administration has approved a health claim for soy based on clinical trials and epidemiological data indicating that high soy consumption is associated with a lower risk of coronary artery disease. Soy products contain a group of compounds called isoflavones, with genistein and daidzein being the most abundant. A number of cardioprotective benefits have been attributed to dietary isoflavones including a reduction in LDL cholesterol, an inhibition of pro-inflammatory cytokines, cell adhesion proteins and inducible nitric oxide production, potential reduction in the susceptibility of the LDL particle to oxidation, inhibition of platelet aggregation and an improvement in vascular reactivity. There is increasing interest in the use of nutrigenomic methods to understand the mechanisms by which isoflavones induce these changes, and in the use of nutrigenetics to understand why the effects vary between individuals. Nutrigenomics is a rapidly growing field making use of molecular biology methodologies, such as microarray technology and proteomics, to study how specific nutrients or diets affect gene expression and cellular protein levels. The analysis of differential gene expression and protein levels in endothelial cells, macrophages and smooth muscle cells is critical to elucidating the sequence of events leading to the formation of atherosclerotic lesions, and to understanding the potential anti-atherogenic properties of soy isoflavones. An increasing number of studies demonstrate a significant impact of genetic variation on changes in cardiovascular risk factors in response to dietary intervention. Nutrigenetic effects of this type have recently been reported for dietary isoflavones, and may help to explain some of the disparities in the current literature concerning isoflavones and cardiovascular health.