Coronary endothelial function regulation by wall shear stress (WSS), the frictional force of blood exerted against the vessel wall, can help explain the focal propensity of plaque development in an environment of systemic atherosclerosis risk factors. Sustained abnormal pathologic WSS leads to a proatherogenic endothelial cell phenotype, plaque progression and transformation, and adaptive vascular remodeling in site-specific areas. Assessing dynamic coronary plaque compositional changes in vivo remains challenging; however, recent advances in intravascular image acquisition and processing may provide swifter WSS calculations and make possible larger prospective investigations on the prognostic value of WSS in patients with coronary atherosclerosis.