In conclusion, we have demonstrated as a proof of concept the H2-driven reduction of flavins to promote selective biocatalytic reduction and oxidation reactions. The presented flavin recycling by H2 oxidation enabled the efficient reduction of activated alkenes, the selective hydroxylation of alkanes and the asymmetric epoxidation of styrene. The cofactor regeneration by a hydrogenase resulted in 100% atom efficiency without by-products, with a high turnover rate of up to 20.3 s -1 and a total turnover number of up to 46000. The electron delivery strategy circumvents NAD(P)H as the reductant and shortens previous multi-protein systems with reductases to a two-enzyme system. The O2 tolerance of the hydrogenase allowed aerobic reactions with a monooxygenase, whereas the spontaneous aerobic reoxidation of FMNH2 to H2O2 fueled peroxygenase-catalyzed hydroxylation reactions. A general applicability of the NAD(P)H-free, H2-driven flavin regeneration system was demonstrated by using different oxidoreductases (TsOYE, StyA and UPO) and substrates (e.g. 2-methylcyclohexenone, styrene, ethylbenzene). The ability to use H2 as a fuel for flavin recycling opens up opportunities for highly atom-efficient biocatalysis, providing a versatile platform for future biotransformations with flavin-and H2O2-dependent enzymes.