A variety of systemic risk factors, including smoking, hypertension, hyperlipidemia and diabetes have been found to promote atherosclerosis. Although these elements affect blood vessels equally, clinically significant lesions develop at predictable locations, i.e., major branch points and bifurcations. This suggests that the development of clinically significant atherosclerotic plaques involves a complex interplay between vascular anatomy, vascular biology and hemodynamic forces. Cyclic strain, circumferential pulsatile pressure exerted upon a vessel wall, has been found to cause changes in endothelial cells that tend to disfavor atherosclerosis formation. Cultured endothelial cells have been shown to migrate, proliferate and alter cytoskeletal alignment in response to cyclic strain. Levels of macromolecules such as prostacyclin, endothelin, nitric oxide and tissue plasminogen activator have been found to be altered by cyclic strain. Additionally, cyclic strain has been shown to stimulate expression of cellular adhesion molecules such as ICAM-1 and intracellular second messenger systems such as the adenylate cyclase-cAMP, diacylglycerol-IP3, and protein kinase C pathways. This article reviews the most current pertinent literature and summarizes the presently known effects of cyclic strain on endothelial cells.