There is no mammalian life without oxygen. At the same time, oxygen can be toxic. This paper focuses on extrapulmonary manifestations of oxygen toxicity. Hyperbaric and normobaric applications of oxygen are relevant to the anesthesiologist and carry different risks of oxygen toxicity. Normobaric O2 is tolerated for relatively long periods and has no acute sequelae. Chronic exposure to normobaric O2 will increase the concentration of oxygen radicals in the tissues and produce organ damage. This has to be weighed against the risk of withholding possibly life-saving oxygen therapy. High FiO2 can be used to increase plasma dissolved oxygen to offset low hemoglobin based oxygen transport capacity of blood during acute pre- or intraoperative normovolemic hemodilution with the aim of reducing allogeneic transfusion requirements. Administration of hyperbaric oxygen can be followed by a spectrum of neurologic disturbances leading to frank convulsions. The mechanism leading to cerebral seizure activity is not fully understood but is possibly linked to oxygen radical production and the L-Arginine-NO system.