The concentration of molecular oxygen (O2) began to increase in the Earth's atmosphere approximately two billion years ago. Its presence posed a threat to anaerobes but also offered opportunities for improved energy conservation via aerobic respiration. The ability to sense environmental O2 thus became, and remains, important for many bacteria, both for protection and switching between anaerobic and aerobic respiration. Utilizing an iron–sulfur cluster as the sensor of O2 exploits the ability of O2 to oxidize the iron–sulfur cluster, ultimately resulting in cluster disassembly. When utilizing heme as the sensor, the capacity of O2 to form a reversible Fe–O2 bond or alternatively the oxidation of the heme iron atom itself is used to detect O2 and switch regulators between active and inactive forms.