This paper reviews our efforts to simulate methanol synthesis from CO and H2 on defective ZnO surfaces using advanced molecular dynamics techniques. This apparently simple chemical reaction occurring on a seemingly well-defined surface appears to be astonishingly complex. First of all, the preferred oxidation state of F centers at the polar oxygen terminated surface is found to be dictated by the chemical composition and the thermodynamic properties of the gas phase in contact with . Secondly, reaction intermediates and pathways along the catalytic cycle taking place at or close to these defects are found to depend in a sensitive way on their oxidation state. Thirdly, it is seen that the gas phase close to the catalytic surface might be transiently involved in some of the reaction steps in a non-trivial manner. Last but not least, the scenario is found to be greatly enriched upon involving copper clusters on polar ZnO surfaces in view of utmost strong metal-support interactions (SMSIs), which are directly related to the polar nature of . Taken together, an unexpectedly rich picture is unveiled by the molecular dynamics approach to computational heterogeneous catalysis when applied to methanol synthesis on bare ZnO.