DFT/BP86/TZVP and DFT/B3LYP/TZVP have been used to investigate systematically the reaction pathways associated with the H-transfer step, which is the rate-determining step of the reaction HCOO- reversible arrow CO2 + H+ + 2e(-), as catalyzed by metalloenzyme formate dehydrogenase (FDH). Actually, the energetics associated with the transfer from formate to all H (proton or hydride) acceptors that are present within the FDH active site have been sampled. This study points to a viable intimate mechanism in which the metal center mediates H transfer from formate to the final acceptor, i.e. a selenocysteine residue. The Mo-based reaction pathway, consisting of a beta-H elimination to metal with concerted decarboxylation, turned out to be favored over previously proposed routes in which proton transfer occurs directly from HCOO- to selenocysteine. The proposed reaction pathway is reminiscent of the key step of metal-based catalysis of the water-gas shift reaction.