Oxygen treatment is being widely used in intensive care and emergency medicine and is required to maintain aerobic metabolism. It may be administered by nasal cannula, face mask, high-flow therapy, and by ventilation. Under clinical circumstances, blood oxygen concentration is not relevantly increased above a partial pressure of 80 mmHg. Although oxygen therapy is often life-saving, it has recently been shown that its indiscriminate administration may increase morbidity and mortality, presumably due to a formation of reactive-oxygen species.For ventilated critically ill patients the optimal targets need to be further defined but harm has been shown for mild hyperoxia. For patients with acute exacerbation of chronic obstructive lung disease hyperoxia may lead to an increase of hypercarbia. Hyperoxia may increase myocardial necrosis in myocardial infarction. For patients with stroke, data do not show any benefit or harm from oxygen administration.On the other hand, hyperoxia shall be used for treatment in patients with cardiac arrest until return of spontaneous circulation and in patients with carbon monoxide poisoning.For other conditions, no benefit has been shown for hyperoxia, but undoubtedly, hypoxemia must be avoided, as well. Therefore, a normoxic oxygenation strategy should be employed. The optimal oxygenation targets for distinct conditions need to be further defined.