The discovery of vascular endothelial growth factor (VEGF) changed the field of angiogenesis. We have learned that VEGF has broader actions than merely a driver of tumor angiogenesis, particularly that VEGF controlled several fundamental functions and properties of endothelial cells and nonendothelial cells. The lung is one of the main organs where VEGF controls several crucial physiological functions. These actions rely on tightly regulated temporal and concentration gradients of VEGF and VEGF receptor expression in the lung. Excessive or diminished VEGF have been linked to abnormal lung phenotypes and, in humans, linked to several diseases. The beneficial and detrimental actions of VEGF underscore that therapeutic targeting of VEGF in disease has to carefully consider the lung biology of VEGF.