Coronary artery bifurcations are susceptible to atherosclerosis as a result of the unique local flow patterns and the subsequent endothelial shear stress (ESS) environment that are conducive to the development of plaques. Along the lateral walls of the main vessel and side branches, a distinct flow pattern is observed with local low and oscillatory ESS, while high ESS develops at the flow divider (carina). Histopathologic studies have shown that the distribution of plaque at bifurcation regions is related to the local ESS patterns. The local ESS profile also influences the outcome of percutaneous coronary interventions in bifurcation lesions. A variety of invasive and non-invasive imaging modalities have enabled 3D reconstruction of coronary bifurcations and thereby detailed local ESS assessment by computational fluid dynamics. Highly effective strategies for treatment and ultimately prevention of atherosclerosis in coronary bifurcations are anticipated with the use of advanced imaging and computational fluid dynamic techniques.