The article reviews the effects of disturbed flow on vascular endothelial cells (ECs) and its pathophysiological implications. Disturbed flow, characterized by low and reciprocating shear stress, is common in arterial branches and curvatures, leading to preferential localization of atherosclerotic lesions. This flow pattern induces the activation of genes and proteins that promote atherogenesis, while sustained laminar flow with high shear stress upregulates protective genes and proteins against atherosclerosis. Disturbed flow also contributes to post-surgical neointimal hyperplasia and clinical conditions such as in-stent restenosis, vein bypass graft failure, transplant vasculopathy, and aortic valve calcification. In the venous system, disturbed flow due to reflux, outflow obstruction, and stasis leads to venous inflammation and thrombosis, contributing to chronic venous diseases. Understanding the effects of disturbed flow on ECs can provide insights into the molecular and mechanical bases of vascular diseases and help develop therapeutic strategies. The article discusses the fundamental principles of hemodynamic forces, their impact on vascular homeostasis and remodeling, and the role of disturbed flow in endothelial dysfunction. It also explores the occurrence of disturbed flow in various pathophysiological conditions and its correlation with the development of atherosclerotic lesions and calcific lesions in the aortic valve. Additionally, it examines the contribution of disturbed flow to neointimal hyperplasia and thrombosis in the venous system. Finally, the article reviews in vitro models used to study the effects of disturbed flow on ECs and their morphological, cytoskeletal, and functional responses.The article reviews the effects of disturbed flow on vascular endothelial cells (ECs) and its pathophysiological implications. Disturbed flow, characterized by low and reciprocating shear stress, is common in arterial branches and curvatures, leading to preferential localization of atherosclerotic lesions. This flow pattern induces the activation of genes and proteins that promote atherogenesis, while sustained laminar flow with high shear stress upregulates protective genes and proteins against atherosclerosis. Disturbed flow also contributes to post-surgical neointimal hyperplasia and clinical conditions such as in-stent restenosis, vein bypass graft failure, transplant vasculopathy, and aortic valve calcification. In the venous system, disturbed flow due to reflux, outflow obstruction, and stasis leads to venous inflammation and thrombosis, contributing to chronic venous diseases. Understanding the effects of disturbed flow on ECs can provide insights into the molecular and mechanical bases of vascular diseases and help develop therapeutic strategies. The article discusses the fundamental principles of hemodynamic forces, their impact on vascular homeostasis and remodeling, and the role of disturbed flow in endothelial dysfunction. It also explores the occurrence of disturbed flow in various pathophysiological conditions and its correlation with the development of atherosclerotic lesions and calcific lesions in the aortic valve. Additionally, it examines the contribution of disturbed flow to neointimal hyperplasia and thrombosis in the venous system. Finally, the article reviews in vitro models used to study the effects of disturbed flow on ECs and their morphological, cytoskeletal, and functional responses.