Endothelial dysfunction is a generalized phenomenon detectable at various levels in the vasculature, and is evident very early in the atherosclerotic process. These peculiarities have stimulated the introduction of new non-invasive techniques dedicated to evaluate the vasomotor response of arteries or districts in favourable position in the body (forearm, hand) that may reflect the response of inner arteries otherwise requiring invasive procedures (i.e. coronary arteries). Moreover, these techniques can be theoretically used to detect abnormalities of vasomotor response before a clinical adverse event may occur in subjects prone to vascular accidents with risk factors for atherosclerosis. Of physical stimuli inducing e-NOS activation and subsequent nitric oxide synthesis, the shear stress produced by pulsatile blood flow is the most important. This property is actually used in clinical practice to study the flow-mediated vasodilation (FMD) of the brachial artery. Any condition that reduces the ability of endothelial cells to produce nitric oxide causes endothelial dysfunction, which is directly reflected into a depressed FMD. There is evidence that brachial artery flow-mediated dilation is improved after local as well as systemic exercise, suggesting that the improvement in endothelial function is generalized and documentable in different arterial districts with similar results. Aerobic exercise induces e-NOS expression and improves the endothelial-dependent relaxation in normal as well as cardiac patients. The endothelium-independent vasorelaxation is generally unchanged after chronic conditioning, but this result is not evident in all studies. The improved endothelial vasoreactivity is correlated with enhanced functional capacity after moderate aerobic exercise, suggesting an important pathophysiological role of oxygen transport in exercise tolerance. These beneficial effects has been described in patients with stable heart failure in II and III NYHA functional class and in patients with coronary artery disease with programs different for frequency, duration and intensity. The evaluation of vasomotor reactivity gives promising results in explaining the effects of medications and exercise training. The demonstration that flow-mediated dilation may quantify endothelial dysfunction in subjects with a variety of conditions can be used in clinical practice not only to assess the effects of interventions, but also to provide a preliminary screening in apparently healthy subjects who have an underlying silent coronary artery disease. In cardiac rehabilitation, there are promising results from FMD evaluation in selecting patients who take major benefits in terms of functional capacity and endothelium-dependent vasodilation.