Extreme mountain climbers and patients with stable but severe ventilatory insufficiency (e.g. obesitas hypoventilation-syndrome, scoliosis) sometimes experience a state of severe hypoxemia without any or only mild subjective disturbances. Organ failure is never observed in these periods. On the other hand there are two well documented studies concerning long term oxygen therapy (LTOT) that have shown in hypoxemic COPD-patients (pO 2 lower then 55 mm Hg) a doubling the life expectancy under oxygen. This contradiction can be elucidated if the influence of oxygen on the ventilation is taken into account. These study patients treated with LTOT all had more or less hypercapnia (hypoventilation) due to an overload of their respiratory pump. Oxygen reduces the ventilation (seen as hypercapnia) which leads to an unloading of the respiratory muscles. Later studies to LTOT found a positive correlation between the extent of stable hypercapnia and life expectancy. In this article the physiopathologic background of this findings are discussed. The main parameter of the regulator for the oxygen transport is not pO 2 but the oxygen content. The oxygen content multiplied by cardiac output determines the extent of oxygen delivery. Many regulatory systems (e.g. polyglobuly or expression of oxygen resistant isoenzymes of the respiratory chain) are involved to compensate the hypoxemia associated with hypoventilation which prevents an organ threatening hypoxia. This pathophysiologic finding has important impact on intensive care medicine, which usually takes only pO 2 into account for therapeutic decisions (e. g. high FiO 2 and high pressure support). This sometimes leads to "overtreatment", with possible harm to the patient.