Although mechanisms leading to high altitude illnesses are not yet completely clear some progress has been made. It is well accepted that excessive pulmonary hypertension may lead to HAPE. Furthermore, there is rising evidence about endothelial dysfunction being involved in disease progression. Some cellular and molecular mechanisms of acute (hypobaric) hypoxia, possibly leading to endothelial dysfunction, have been studied in a few experimental and field settings. Paradoxical increase in systemic oxidative stress is seen under hypoxic conditions, such as high altitude stay. Reactive oxygen species (ROS) could be demonstrated in many endothelial disorders and capillary leakage syndromes such as septicaemia, myocardial infarct and stroke. Furthermore, coagulation activation might result from endothelial dysfunction but also amplify endothelial interruption. Still, most of our knowledge concerning effects of hypoxia in general but also concerning oxidative stress is from in vitro studies (e.g. cancer cells).