Preservation of normal endothelial function depends on the bioavailability of nitric oxide (NO). In addition, accumulating evidence suggests that bone marrow-derived circulating progenitor cells (CPCs) are required to maintain the integrity of the vasculature. However, in patients with cardiovascular disease (CVD), the impairment of NO production in conjunction with excessive oxidative stress, results in a decline in NO bioavailability, promotes the loss of endothelial cells by apoptosis and, therefore, results in endothelial dysfunction. Moreover, functional alteration of CPCs might contribute to an impaired endogenous regenerative capacity and lead to further deterioration of vasomotion in different vascular beds in CVD. However, exercise training (ET) has assumed a role in cardiac rehabilitation in CVD since it reduces morbidity and mortality. This has been partially attributed to ET-mediated improvement of endothelial function. At the molecular levels, accumulating evidence suggests that regular physical activity restores the balance between NO production and NO inactivation by ROS. Moreover, ET might have the potential to restore the regenerative capacity of CPCs in CVD. Given the prognostic value of endothelial function further studies are necessary to elucidate whether the ET-induced correction of vasomotion is the key mechanism responsible for the decline in mortality in patients with CVD.