The systemic effects of oxygen deficiency or excess are not thoroughly described. Knowledge is evolving towards the description of beneficial and detrimental effects of both extremes of partial pressure of oxygen (PaO2). The cellular and tissue mediators derived from the modulation of the oxidative tone and the production of reactive oxygen species (ROS) are widely characterized biochemically, but the pathophysiological characterization is lacking. Preclinical models support the use of hypobaric hypoxia preconditioning, based on its beneficial effects on ventricular function or its reduction in infarct size. A very important use of oxygen today is in commercial diving. However, novel clinical indications for oxygen such as the healing of diabetic foot ulcers and bone injury caused by radiotherapy are increasingly used. On the other hand, the modulation of the hypoxic response associated with exposure to high altitude environments (hypobaric), favors Chile and its highlands as a natural laboratory to determine certain cardiovascular, cerebral and metabolic responses in the resident population. Also, the consequences of the intermittent exposure to high altitudes in workers also deserves attention. This review discusses the physiopathological response to hypo and hyperoxemia, associated with environments with different oxygen concentrations, and brings back the concept of oxygen as a pharmacological mediator in extreme environments such as high altitudes and hyperbaric medicine in divers, decompression sickness, osteonecrosis associated with radiotherapy and sudden sensorineural hearing loss.