The endothelium, once thought to be a passive, non-thrombogenic barrier, is now recognized as being a dynamic participant in vascular biology and pathobiology. Part of its dynamic nature is due to the influence of the mechanical environment imposed by the hemodynamics of the vascular system. Over the past two decades much has been learned about the influence of hemodynamics on the vascular endothelium. This has been in part through in vivo experiments; however, in the past 15 years a number of laboratories have turned to the application of in vitro cell culture systems to investigate the influence of flow and cyclic stretch on the biology of vascular endothelium. Taken together these studies demonstrate that flow and the associated shear stress modulate both endothelial cell structure and function. Cell culture studies employing cyclic stretch provide similar evidence. Furthermore, these effects of mechanical environment extend to the gene expression level, with there being a differential regulation of mRNA. A critical question is how does an endothelial cell recognize the mechanical environment in which it resides and, having done so, how is this transduced into the changes in structure and function observed? Although our knowledge of the recognition events remains limited, studies on signal transduction in response to a mechanical stimulus indicate that many of the second messengers known to be triggered by chemical agonists also are involved in transducing a mechanical signal. Over the past 20 years our understanding of the importance of the influence of the mechanical environment imposed by the hemodynamics of the system on vascular endothelial biology, both in the regulation of the normal biology of blood vessels and as a determinant of the distribution and development of atherosclerotic lesions, has grown immensely; however, there is still much to be learned.