SUMMARY. Chronic obstructive pulmonary disease (COPD) is a major health problem worldwide, with increasing prevalence and mortality. 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 on lung development and physiology. VEGF is expressed to varying degrees in different parts of the lung, and it has been shown that differences in its expression play a significant role in the pathophysiology of two major phenotypes of COPD, namely, emphysema and chronic bronchitis. VEGF is known to maintain the homeostasis of the alveolar compartment, and therefore a 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 the alveolar walls to oxidative stress and proteases. The lack of VEGF in emphysema may have implications for its substitution, while its over-expression in chronic bronchitis has led to interventions directed at attenuation of its action. The scope of this review is to summarize from a clinical point of view the role of VEGF in the pathogenesis of COPD, focusing on its diagnostic and therapeutic implications. Pneumon 2008; 21(1):68–76