Scientific understanding of atherogenesis is constantly developing. From Virchow's observations 160 years ago we now recognize the endothelial response to injury as inflammatory, involved in all stages of atherosclerosis. Endothelial activation may cause reversible injury or dysfunction, or lead to irreparable damage. Indeed, early atherosclerosis is reversible. The introduction of genome-wide association testing has furthered the identification of potentially important genetic variants that help explain the heritability of coronary artery disease as well as spontaneous cases of severe coronary artery disease in patients with otherwise minimal risk factors. However, the mechanisms by which many of the newer variants exert their influence remain unknown.