Hemodynamic forces influence functional properties of vascular endothelium. Endothelial cells have a variety of receptors, which sense flow and transmit mechanical signals through mechanosensitive signaling pathways to recipient molecules, that lead to phenotypic and functional changes. Arterial architecture varies greatly exhibiting bifurcations, branch points, and curved regions, which are exposed to various flow patterns. Clinical studies showed that atherosclerotic plaques develop preferentially at arterial branches and curvatures, i.e. in the regions exposed to disturbed flow and shear stress. In the atheroprone regions, the endothelium has a proinflammatory phenotype associated with low nitric oxide production, reduced barrier function, and increased proadhesive, procoagulant, and proproliferative properties. Atheroresistant regions are exposed to laminar flow and high shear stress that induce prosurvival antioxidant signals and maintain the quiescent phenotype in endothelial cells. Indeed, various flow patterns contribute to phenotypic and functional heterogeneity of arterial endothelium whose response to proatherogenic stimuli is differentiated. This may explain the preferential development of endothelial dysfunction in arterial sites with disturbed flow. This article is protected by copyright. All rights reserved.