Molecular oxygen is often represented as a double-edged sword, essential to sustain oxidative phosphorylation that provides the bulk of the cell biological energy, yet toxic. In the current geological era, its proportion in the atmosphere happens to be 20.93%-20.95%, but in past eras, it fluctuated within the 0%-30% range, with different forms of life that could adapt successfully even by using alternative redox sources as hydrogen sulfide. Actually, humans may have lost the ability to adapt to oxygen levels departing consistently from 20.93% to 20.95%. Consequently, either hypoxia or hyperoxia represents potentially lethal situations. Yet, they are more common than suspected. Hypoxia is found in physiological (high altitude, commercial flights, prebirth environment, and physical exercise) and pathological (inflammation, solid cancers, ischemia, as well as in cardiopulmonary, kidney, and neurodegenerative diseases) contexts, whereas hyperoxia, although less frequent, is the most used therapy in pulmonary patients and during anesthesia. The Forum "Oxygen Sensing" contains contributions aimed at clarifying the complex mechanisms underlying the responses to too much and too little oxygen at molecular, cellular, tissue, and body levels, highlighting the oxygen-sensing mechanisms in various districts of the organism. The translational interest of this Forum invests the modulation of the oxygen-sensing activity and sensitivity as a therapeutic perspective in the treatment of several diseases. Antioxid. Redox Signal. 37, 863-866.