Endothelial dysfunction in the extrapulmonary circulation has been linked to cardiovascular disease. Recent investigations have revealed that in the airway circulation, cigarette smoking, chronic obstructive pulmonary disease (COPD), and asthma are also accompanied by endothelial dysfunction. Inhaled glucocorticosteroids can partially or fully restore normal endothelium-dependent vasodilation in these conditions, thereby identifying the airway endothelium as a novel therapeutic target in the treatment of airway disease. The role of the defective endothelium-dependent vasodilation in the pathophysiology in asthma and COPD is still subject to speculation. However, there appears to be an association between COPD and extrapulmonary vascular dysfunction, and the possibility exists that the use of inhaled glucocorticosteroids has a beneficial effect on cardiovascular disease in COPD as suggested by database studies showing that inhaled glucocorticosteroids reduce the incidence of nonfatal and fatal cardiovascular events in COPD.