Flow-mediated endothelial mechanotransduction is a critical process in vascular physiology, involving the transmission of hemodynamic forces to endothelial cells, which then convert these mechanical signals into biochemical and gene regulatory responses. This review discusses the mechanisms by which endothelial cells respond to blood flow, focusing on hemodynamic shear stress. The endothelium, located between blood and the vascular wall, is exposed to significant fluid forces, leading to mechanical responses that regulate vascular tone, arterial structure, and the localization of atherosclerotic lesions. Hemodynamic forces influence endothelial biology through direct shear stress and indirect chemical modifications at the endothelial surface. The mechanisms of mechanotransduction involve the cytoskeleton, which transmits mechanical forces and facilitates intracellular signaling. The cytoskeleton, including actin filaments, microtubules, and intermediate filaments, plays a key role in force transmission and cell shape changes in response to flow. Endothelial cells exhibit morphological changes in response to shear stress, with alignment reflecting the direction and magnitude of the flow. The cytoskeleton also enables the transmission of mechanical forces throughout the cell, with integrins and other membrane proteins playing a crucial role in this process. The endothelial surface's topography influences hemodynamic forces, and detailed analyses of flow characteristics help estimate shear stress distribution. Signal filtering and adaptation mechanisms allow endothelial cells to respond to mechanical stimuli, with adaptation involving feedback inhibition and signal filtering. Mechanoreceptors, such as ion channels and integrins, are involved in transducing mechanical signals into biochemical responses. Stretch-activated and shear stress-activated ion channels are key components of mechanotransduction, with their activity regulated by intracellular calcium levels and other signaling pathways. The cytoskeleton's role in mechanotransduction is further supported by studies showing that mechanical forces can alter cytoskeletal structure and function. Overall, the complex interplay between mechanical forces and endothelial cells is essential for maintaining vascular homeostasis and preventing pathological conditions such as atherosclerosis.Flow-mediated endothelial mechanotransduction is a critical process in vascular physiology, involving the transmission of hemodynamic forces to endothelial cells, which then convert these mechanical signals into biochemical and gene regulatory responses. This review discusses the mechanisms by which endothelial cells respond to blood flow, focusing on hemodynamic shear stress. The endothelium, located between blood and the vascular wall, is exposed to significant fluid forces, leading to mechanical responses that regulate vascular tone, arterial structure, and the localization of atherosclerotic lesions. Hemodynamic forces influence endothelial biology through direct shear stress and indirect chemical modifications at the endothelial surface. The mechanisms of mechanotransduction involve the cytoskeleton, which transmits mechanical forces and facilitates intracellular signaling. The cytoskeleton, including actin filaments, microtubules, and intermediate filaments, plays a key role in force transmission and cell shape changes in response to flow. Endothelial cells exhibit morphological changes in response to shear stress, with alignment reflecting the direction and magnitude of the flow. The cytoskeleton also enables the transmission of mechanical forces throughout the cell, with integrins and other membrane proteins playing a crucial role in this process. The endothelial surface's topography influences hemodynamic forces, and detailed analyses of flow characteristics help estimate shear stress distribution. Signal filtering and adaptation mechanisms allow endothelial cells to respond to mechanical stimuli, with adaptation involving feedback inhibition and signal filtering. Mechanoreceptors, such as ion channels and integrins, are involved in transducing mechanical signals into biochemical responses. Stretch-activated and shear stress-activated ion channels are key components of mechanotransduction, with their activity regulated by intracellular calcium levels and other signaling pathways. The cytoskeleton's role in mechanotransduction is further supported by studies showing that mechanical forces can alter cytoskeletal structure and function. Overall, the complex interplay between mechanical forces and endothelial cells is essential for maintaining vascular homeostasis and preventing pathological conditions such as atherosclerosis.