Oxygen (O(2)) is the most frequently used pharmaceutical in anesthesiology and intensive care medicine: Every patient receives O(2) during surgery or during a stay in the intensive care unit. Hypoxia and hypoxemia of various origins are the most typical indications which are mentioned in the prescribing information of O(2): the goal of the administration of O(2) is either an increase of arterial O(2) partial pressure in order to treat hypoxia, or an increase of arterial O(2) content in order to treat hypoxemia. Most of the indications for O(2) administration were developed in former times and have seldom been questioned from that time on as the short-term side-effects of O(2) are usually considered to be of minor importance. As a consequence only a small number of controlled randomized studies exist, which can demonstrate the efficacy of O(2) in terms of evidence-based medicine. However, there is an emerging body of evidence that specific side-effects of O(2) result in a deterioration of the microcirculation. The administration of O(2) induces arteriolar constriction which will initiate a decline of regional O(2) delivery and subsequently a decline of tissue oxygenation. The aim of the manuscript presented is to discuss the significance of O(2) as a pharmaceutical in the clinical setting.