Pulmonary edema is a life-threatening complication of critical illness. Identification of the underlying mechanisms of pulmonary edema is a prerequisite for the development of adequate treatment. The initial description of fluid transportation across capillaries (Starling's law) while of critical importance, did not provide full insight into the underlying pathophysiology of vascular leakage. Pulmonary edema can be differentiated into two distinct categories based on the Starling theory; the high-permeability type is attributed to inflammatory changes occurring in conditions such as the adult respiratory distress syndrome (ARDS) and the cardiogenic type is characterized by an imbalance in the Starling hydrostatic forces and occurs in acute or decompensated heart failure. However, it has long been recognized that there is significant overlap between the various types of pulmonary edema, raising important questions regarding the role of novel mechanisms that may contribute to the development of interstitial and alveolar leakage. Recently, several studies on VEGF, an angiogenic growth factor which affects endothelial permeability, have identified this molecule as a potential regulator of vascular leakage and repair in pulmonary edema. We review here the underlying the mechanisms by which VEGF may do this and will discuss the still unanswered questions regarding vascular pharmacology in the setting of pulmonary edema.