--- - |2+ Abstract When lung cells experience hypoxia, the functional response, termed hypoxic pulmonary vasoconstriction, activates a multitude of pathways with the goal of optimizing gas exchange. While previously controversial, overwhelming evidence now suggests that increased reactive oxygen species – produced at complex III of the mitochondrial electron transport chain and released into the intermembrane space – is the cellular oxygen signal responsible for triggering hypoxic pulmonary vasoconstriction. The increased reactive oxygen species (ROS) activate many downstream targets that ultimately lead to increased intracellular ionized calcium concentration and contraction of pulmonary arterial smooth muscle cells. While the specific targets of ROS signals are not completely understood, it is clear that this signalling pathway is critical for development and for normal lung function in newborns and adults. - The Journal of Physiology, EarlyView.