Chronic obstructive pulmonary disease (COPD) is a major worldwide health problem that has an increasing prevalence and mortality. However, the exact mechanism of initiation and progression of this disease has not been fully elucidated. Vascular endothelial growth factor (VEGF) is a potent mediator of angiogenesis, which has multiple effects in lung development and physiology. VEGF is expressed in several amounts or parts in the lung, while it has been shown that differences in its expression play a significant role in the pathophysiology of two major phenotypes of COPD (emphysema and chronic bronchitis). VEGF is known to maintain the homeostasis of alveolar compartment, and therefore the decrease in VEGF expression affects the pathogenesis of emphysema. In emphysema, pulmonary endothelial cell apoptosis via reduction in VEGF activity causes alveolar epithelial cell apoptosis, thereby increasing the sensitivity of alveolar walls to oxidative stress and proteases. Therefore, the lack of VEGF in emphysema may provide implications for its substitution, whereas its over-expression in chronic bronchitis has led to interventions for the attenuation of its action. The scope of the present review is to summarize from a clinical point of view the role of VEGF in the pathogenesis of COPD and focus on its diagnostic and therapeutic implications.