Methane has long been known to be used as a carbon and energy source by some aerobic alpha- and delta-proteobacteria. In these organisms the metabolism of methane starts with its oxidation with O(2) to methanol, a reaction catalyzed by a monooxygenase and therefore restricted to the aerobic world. Methane has recently been shown to also fuel the growth of anaerobic microorganisms. The oxidation of methane with sulfate and with nitrate have been reported, but the mechanisms of anaerobic methane oxidation still remains elusive. Sulfate-dependent methane oxidation is catalyzed by methanotrophic archaea, which are related to the Methanosarcinales and which grow in close association with sulfate-reducing delta-proteobacteria. There is evidence that anaerobic methane oxidation with sulfate proceeds at least in part via reversed methanogenesis involving the nickel enzyme methyl-coenzyme M reductase for methane activation, which under standard conditions is an endergonic reaction, and thus inherently slow. Methane oxidation coupled to denitrification is mediated by bacteria belonging to a novel phylum and does not involve methyl-coenzyme M reductase. The first step in methane oxidation is most likely the exergonic formation of 2-methylsuccinate from fumarate and methane catalyzed by a glycine-radical enzyme.