The review focuses on the biological machines that oxidize, reduce, and interconvert one-carbon compounds. The focus is on the unusual cofactors and enzymes in methanogens and acetogens that are involved in anaerobic one-carbon metabolism, which is key to the globla carbon cycle. A variety of autotrophic anaerobes can fix CO₂ into organic carbon as well as use the reduction of CO₂ as a source of energy. CO dehydrogenase, formate dehydrogenase, and formylmethanofuran dehydrogenase are metalloenzymes that reduce CO₂ to the formate oxidation level (CO, formate, or formylmethyanofuran). At the formate level, the one-carbon compounds are converted to a cofactor-bound form, either the formyl- or methenyl tetrahydromethanopterin or tetrahydrofolate derivatives, before they undergo further reduction. The next stage, reduction from the formate to the formaldehyde level, is accomplished by either methylenetetrahydrofolate or methylenetetrahydromethopterin dehydrogenase. Metalloenzymes again enter the picture at the methanol oxidation level. Afer reduction of the methylene derivatives to methyltetrahydrofolate or methyltetrahydromethanopterin by a reductase, cobalamin-dependent methyltransferases attach the methyl group to the cobalt as enzyme-bound methyl-cob(III)amide. The most reduced one-carbon compounds are at the methane level. Reduction of the methyl-Co(III) derivatives to methane is accomplished by methyl coenzyme M reductase. Alternatively, the methyl group is reduced by acetyl-CoA synthase to acetyl-CoA. The oxidation of methane back to CO₂ is initiated by methane monooxygenase, while there are various microbes that can use acetyl-CoA as an energy source.