Newcomer SC, Thijssen DH, Green DJ. Effects of exercise on endothelium and endothelium/smooth muscle cross talk: role of exercise-induced hemodynamics. J Appl Physiol 111: 311-320, 2011. First published March 24, 2011; doi:10.1152/japplphysiol.00033.2011.-Physical activity, exercise training, and fitness are associated with decreased cardiovascular risk. In the context that a risk factor "gap" exists in the explanation for the beneficial effects of exercise on cardiovascular disease, it has recently been proposed that exercise generates hemodynamic stimuli which exert direct effects on the vasculature that are anti-atherogenic. In this review we briefly introduce some of the in vitro and in vivo evidence relating exercise hemodynamic modulation and vascular adaptation. In vitro data clearly demonstrate the importance of shear stress as a potential mechanism underlying vascular adaptations associated with exercise. Supporting this is in vivo human data demonstrating that exercise-mediated shear stress induces localized impacts on arterial function and diameter. Emerging evidence suggests that exercise-related changes in hemodynamic stimuli other than shear stress may also be associated with arterial remodeling. Taken together, in vitro and in vivo data strongly imply that hemodynamic influences combine to orchestrate a response to exercise and training that regulates wall stress and peripheral vascular resistance and contributes to the antiatherogenic impacts of physical activity, fitness, and training.