Density functional theory (DFT) calculations show that hydrogen bonded neighbors can assist or hinder alcohol dehydrogenation on a metal catalyst. This critical role on C–H and O–H bond ruptures is addressed through two main cases: (i) the intermolecular hydrogen bond in the coadsorption of ethanol and water, and (ii) the intramolecular hydrogen bonds in glycerol. In the case of ethanol dehydrogenation, we show that the best catalyst is not bare Rh(111) but a surface with preadsorbed water or ethanol, the reactant ethanol being hydrogen bonded to the chemisorbed molecule, in a favorable configuration for O–H dissociation at the Rh surface. In addition, the intrinsic C–H/O–H reactivity is altered by hydrogen bonded neighbors. The O–H bond dissociation barrier is lowered by up to 0.25 eV. Conversely, the C–H bond scission is slightly inhibited (barrier increased by 0.1 eV maximum). As a result, O–H dissociation becomes favored. Glycerol reactivity is modulated by intramolecular H-bonds, with an additional constraint imposed by the carbon skeleton. Its reactivity is different from that of an isolated ethanol molecule, again with a preference for O–H cleavage.