Some . billion years ago, the great oxygenation event (GOE) led to a -fold rise in atmospheric oxygen [O ], killing most species on Earth. In spite of the tendency to produce toxic reactive oxygen species (ROS), the highly exergonic reduction of O made it the ideal biological electron acceptor. During aerobic metabolism, O is reduced to water liberating energy, which is coupled to adenosine triphosphate (ATP) synthesis. Today, all organisms either aerobic or not need to deal with O toxicity. O -permeant organisms need to seek adequate [O ], for example, aquatic crustaceans bury themselves in the sea botom where O is scarce. Also, the intestinal lumen and cytoplasm of eukaryotes is a microaerobic environment where many facultative bacteria or intracellular symbionts hide from oxygen. Organisms such as plants, ish, reptiles and mammals developed O -impermeable epithelia, plus specialized external respiratory systems in combination with O -binding proteins such as hemoglobin or leg-hemoglobin control [O ] in tissues. Inside the cell, ROS production is prevented by rapid O consumption during the oxidative phosphorylation (OxPhos) of ATP. When ATP is in excess, OxPhos becomes uncoupled in an efort to continue eliminating O . Branched respiratory chains, unspeciic pores and uncoupling proteins (UCPs) uncouple OxPhos. One last line of resistance against ROS is deactivation by enzymes such as super oxide dismutase and catalase. Aerobic organisms proit from the high energy released by the reduction of O , while at the same time they need to avoid the toxicity of ROS.