Alveolar hypoxia has two effects in the pulmonary circulation – vasoconstriction and pulmonary vascular remodelling. Hypoxic pulmonary vasoconstriction (HPV) is essential for adaptation of blood perfusion to regional ventilation. Under conditions of regional alveolar hypoxia it reduces blood flow to hypoxic areas, thereby increasing the perfusion of better ventilated regions. Perturbations to HPV, which may occur in pneumonia, the adult respiratory distress syndrome, and liver failure, can result in severe arterial hypoxemia. Under conditions of generalized hypoxia, however, HPV increases pulmonary vascular resistance and thus causes acute pulmonary hypertension. If alveolar hypoxia becomes chronic, in addition to vasoconstriction a vascular remodelling process is induced which morphologically narrows the vascular lumen and fixes pulmonary hypertension. Moreover, effects of hypoxia can be relevant during ischemia and reperfusion. Despite intensive research, the underlying mechanisms of HPV, pulmonary vascular remodelling and ischemia-reperfusion have not been fully elucidated yet. On the level of the oxygen sensors reactive oxygen species (ROS) producing systems have been proposed to be the initial part of a reaction chain leading to these physiological and pathophysiological effects. However, with regard to ROS there is still discussion whether an increase or a decrease of ROS under hypoxia induces HPV and vascular remodelling. With regard to its sources mitochondria as well as NAD(P)H-oxidases have been suggested. Against this background we provided evidence that NADPH oxidases as well as mitochondria contribute to the regulation of HPV by an increase of ROS and that the pulmonary vascular remodelling may be dependent on the NADPH oxidase isoform NOX4. In contrast, the phagocytic NADPH oxidase isoform NOX2 in endothelial cells is a critical protein complex for the ischemia-reperfusion induced lung injury. Thus, mitochondria and NADPH oxidases maybe targeted to improve deteriorated gas exchange, treat hypoxia-induced pulmonary hypertension and prevent ischemia-reperfusion induced oedema during lung transplantation.