The B12 or cobalamin coenzymes are complex macrocycles whose reactivity is associated with a unique cobalt-carbon bond. The two biologically active forms are MeCbl and AdoCbl and their closely related cobamide forms. MeCbl participates as the intermediate carrier of activated methyl groups. During the catalytic cycle the coenzyme shuttles between MeCbl and the highly nucleophilic cob(I)alamin form. Examples of MeCbl-dependent enzymes include methionine synthase and Me-H4-MPT: coenzyme M methyl transferase. AdoCbl functions as a source of carbon-based free radicals that are unmasked by homolysis of the coenzyme's cobalt-carbon bond. The free radicals are subsequently used to remove non-acid hydrogen atoms from substrates to facilitate a variety of reactions involving cleavage of carbon-carbon, carbon-oxygen and carbon-nitrogen bonds. Most reactions involve 1,2 migrations of hydroxy-, amino- and carbon-containing groups, but there is also one class of ribonucleotide reductases that uses AdoCbl. The structures of two cobalamin-dependent enzymes, methionine synthase and methylmalonyl-CoA mutase, have been solved. In both cases the cobalt is co-ordinated by a histidine ligand from the protein. The significance of this binding motif is presently unclear since in other cobalamin-dependent enzymes spectroscopic evidence suggests that the coenzyme's nucleotide 'tail' remains co-ordinated to cobalt when bound to the protein.