[4Fe–4S]2+ clusters are used by very diverse types of bacterial sensors for response to oxygen, including DNA-binding proteins of the CRP/FNR family and sensor kinases like NreB. In NreB the cluster is bound by an input domain of the PAS type. The [4Fe–4S]2+ cluster of NreB responds to O2 by degradation to a [2Fe–2S]2+ cluster which is labile and decomposes. NreB constitutes together with AirS the NreB/AirS family of bacterial sensor kinases that contain PAS or GAF domains for binding of [4Fe–4S]2+ or [2Fe–2S]2+ clusters and oxygen sensing. The NreB/AirS family is related to the FixL sensor kinases that use hemeB binding PAS domains for oxygen sensing.