Cell respiration is mainly catalysed by the so-called heme–copper oxygen reductases, which are characterised by a binuclear active site containing an oxygen-binding heme group and a nearby copper ion. The copper ion is ligated by three histidine residues, one of which is covalently bonded to a tyrosine residue and takes active part in the reduction of O2 to water. In addition, a low-spin heme is located adjacent to the oxygen-binding heme serving as the immediate electron donor to the binuclear site. Binding of O2 is followed by a “concerted” four-electron reduction confined within the binuclear site, leaving the site in a highly oxidised configuration, akin to the classical Compound I of the peroxidases and catalase. The catalytic cycle is then completed by sequential additions of four electrons to the binuclear centre, one at a time, to end up in the initial reduced state that binds the next O2. These four electron transfers are intimately coupled to proton translocation across the mitochondrial (or bacterial) membrane, which gives the function of the heme–copper oxygen reductases an additional intriguing dimension.