Ultrathin metal oxide films have attracted considerable interest in recent years as versatile substrate for the design of nanocatalytic model systems. In particular, it has been proposed theoretically and confirmed experimentally that the electronic structure of adsorbates can be influenced by the layer thickness and the stoichiometry, i.e., the type and number of defects, of the oxide film. This has important consequences on the chemical reactivity of the oxide surface itself and of oxide supported metal clusters. It also opens new possibilities to influence and to control chemical reactions occurring at the surface of these systems. The present feature focuses on very recent experiments that illustrate the effects of a proper adjustment of layer thickness and composition of ultrathin MgO(100) films on chemical transformations. On the magnesia surface itself, the photodissociation dynamics of methyl iodide molecules is investigated via femtosecond-laser pump–probe mass spectrometry. Furthermore, the catalytic oxidation of carbon monoxide at mass-selected Au20 clusters deposited on magnesia is explored through temperature programmed reaction measurements. In the latter case, detailed first principles calculations are able to correlate the experimentally observed reactivity with structural dimensionality changes that are induced by the changing thickness and composition of the magnesia support.