The identification of pathogenic risk factors for atherosclerosis, such as hyperlipidemia, hypertension, and diabetes, has led to modifications in lifestyle and novel therapies that have had a significant impact on the morbidity and mortality associated with atherosclerosis-related diseases. However, despite such advances, these diseases remain highly prevalent in industrialized nations, and the recent increase in obesity and diabetes, especially in children, forecasts a resurgence in the incidence of atherosclerosis-associated morbidity. Over the last three decades, the field has rediscovered the critical role that inflammation plays in the pathogenesis of atherosclerosis. An important component of inflammation is the emigration of leukocytes from the blood into tissues. The vascular endothelium, being situated at the interface between the blood and tissues, has important regulatory functions in atherosclerosis. In normal arteries, the endothelium has homeostatic functions, including nonadhesive and antithrombotic properties, and it provides a barrier to plasma protein and lipoprotein extravasation (1). Endothelial cells (ECs) are not a passive impermeable “Teflon-like” lining, but are active cells, which respond to diverse blood- and tissue-derived stimuli. For example, in response to the repertoire of local cytokines and modified lipoprotein components, ECs synthesize and present molecules that regulate the recruitment of distinct leukocyte subpopulations to atherosclerotic lesions. Profound and diverse changes in EC phenotype in response to different cytokines have been referred to as EC activation (2). ECs also can respond to external mechanical forces, including hemodynamic forces of blood (3). This is probably why atherosclerotic lesions initially form at sites of arterial branches and curvatures. These regions have unique hemodynamics and EC gene expression patterns that influence signaling, the cellular composition of intimal cells, and responses to systemic risk factors for atherosclerosis.