ABSTRACTA review is presented of the physical principles governing the distribution of blood flow and blood pressure in the vascular system. The main factors involved are the pulsatile driving pressure generated by the heart, the flow characteristics of blood, and the geometric structure and mechanical properties of the vessels. The relationship between driving pressure and flow in a given vessel can be understood by considering the viscous and inertial forces acting on the blood. Depending on the vessel diameter and other physical parameters, a wide variety of flow phenomena can occur. In large arteries, the propagation of the pressure pulse depends on the elastic properties of the artery walls. In the microcirculation, the fact that blood is a suspension of cells strongly influences its flow properties and leads to a nonuniform distribution of hematocrit among microvessels. The forces acting on vessel walls include shear stress resulting from blood flow and circumferential stress resulting from blood pressure. Biological responses to these forces are important in the control of blood flow and the structural remodeling of vessels, and also play a role in major disease processes including hypertension and atherosclerosis. Consideration of hemodynamics is essential for a comprehensive understanding of the functioning of the circulatory system. © 2016 American Physiological Society. Compr Physiol 6:975‐1003, 2016.