As described in Chap. 1 , HP exists within a fluid at rest in equilibrium and any difference in HP between two points in space would drive the fluid to flow along the pressure gradient from the higher to lower pressure point. For this reason, many types of cells in different organs including those of the cardiovascular and skeletal systems are constantly subjected to both fluid flow (and associated shear stress) and HP simultaneously. Since 1980’s the advancement in cell cultures allowed investigators in the field of fluid mechanics to study the link between fluid flow-induced shear stress and vascular health. Moreover, similar experimental approaches have been utilized to expose bone cell cultures to fluid flow and study the century-old theory that the skeletal tissues adapt to mechanical loading. To a lesser extent, investigators also examined the effects of physiological level HP on these cells. In this chapter, we will review the anatomy, physiology, and cellular composition to explore the biomechanical environment of the cells of these organs. We will then review the in vitro studies that aim to understand the role of flow-induced shear stress and HP in pathophysiology of vascular and skeletal organs.