Numerous aspects of vascular homeostasis are modulated by nitric oxide and reactive oxygen species (ROS). The production of these is dramatically influenced by mechanical forces imposed on the endothelium and vascular smooth muscle. In this review, we will discuss the effects of mechanical forces on the expression of the endothelial cell nitric oxide synthase, production of ROS and modulation of endothelial cell glutathione. We will also review data that exercise training in vivo has a similar effect as laminar shear on endothelial function and discuss the clinical relevance of these basic findings.