The article reviews the role of mechanical forces, particularly blood flow, in vascular physiology and atherogenesis. Blood flow, driven by blood pressure, exerts circumferential stretch on endothelial cells (ECs) and vascular smooth muscle cells (VSMCs), influencing vessel development, diameter regulation, and disease progression. Fluid shear stress, a key component of blood flow, is crucial for embryonic vascular development and adult vascular physiology. However, disturbed flow patterns, such as low flow, flow separation, and turbulence, promote atherosclerosis by inducing chronic inflammation and vascular dysfunction. The review discusses the mechanisms by which ECs and VSMCs respond to mechanical forces, including the activation of signaling pathways, gene expression, and extracellular matrix remodeling. It also highlights the importance of specific mechanotransducers, such as adhesion receptors, cytoskeleton, and luminal membrane proteins, in mediating these responses. The article concludes by emphasizing the need for further research to identify all EC-specific shear sensors and understand how these signals interact with systemic risk factors to promote disease progression.The article reviews the role of mechanical forces, particularly blood flow, in vascular physiology and atherogenesis. Blood flow, driven by blood pressure, exerts circumferential stretch on endothelial cells (ECs) and vascular smooth muscle cells (VSMCs), influencing vessel development, diameter regulation, and disease progression. Fluid shear stress, a key component of blood flow, is crucial for embryonic vascular development and adult vascular physiology. However, disturbed flow patterns, such as low flow, flow separation, and turbulence, promote atherosclerosis by inducing chronic inflammation and vascular dysfunction. The review discusses the mechanisms by which ECs and VSMCs respond to mechanical forces, including the activation of signaling pathways, gene expression, and extracellular matrix remodeling. It also highlights the importance of specific mechanotransducers, such as adhesion receptors, cytoskeleton, and luminal membrane proteins, in mediating these responses. The article concludes by emphasizing the need for further research to identify all EC-specific shear sensors and understand how these signals interact with systemic risk factors to promote disease progression.