Density Functional Theory (DFT) calculations show on two examples how catalytic reactivity qualitatively depends on the environment of the active sites. The example of butadiene selective hydrogenation to butenes on Pt or Pd first illustrates how alloying this catalytically active metal with a non- or less reactive elements (Sn or Au, respectively) allows weaker catalyst–molecule interactions and favors the desorption of butenes. It also shows that, from this weakening of the interactions, new reaction pathways are opened and non-selective pathways through a metallacycle intermediate are disadvantaged. Both effects concur on PtSn for an improved selectivity in butenes, while on the PdAu alloy, the gain in selectivity is explained mainly by the easier butene desorption. The dehydrogenation of ethanol on Rh and Pt surfaces shows how co-adsorbates, as water solvent molecules, can interfere with the catalytic elementary steps, assisting OH bond breaking and disadvantaging Csingle bondH dissociation. The balance between these two effects is metal dependent. Ethanol interacts by a strong H-bond with the H2O pre-covered surface, in a more stabilizing way than for the simple adsorption on the bare metal. The surface H2O (or surface-OH) complex can hence be seen as the true active site for the reaction. It is hence important to include the influence of the environment, from the surface part or from the reactant part, for an accurate modeling of heterogeneous catalytic reactions.