Hemodynamic mechanisms for the initiation and progression of carotid bifurcation atherosclerotic occlusive disease have been extensively researched during the past few decades. Attention has focused on the carotid bulb, or sinus, where most atherosclerotic plaques are found. Herein, the authors review the seminal works that have led to an understanding of not only complex local hemodynamics but also the elicited specific biologic response. In addition, new analysis of the age-dependent morphologic maturation of the human carotid bifurcation is unveiled. Understanding the role of hemodynamics in atherogenesis may lead to the improvement of minimally invasive endovascular therapy and noninvasive strategies.