Oxygen vacancies on metal oxide surfaces create active sites for catalytic processes, ranging from selective oxidation of alkenes to photocatalytic decomposition of water. Experimentally, there are numerous challenges associated with fully characterizing the role of oxygen vacancies in bulk systems. We present a bottom-up approach, probing the structures and electronic properties of small metal oxide clusters, and relating these properties to chemical reactivity. The work presented focuses on unary and binary Group 6 metal oxides (Mo and W) and their reactivity toward H2O and CO2. We additionally highlight more recent studies on binary Group 5/Group 6 metal oxides. (C) 2011 Elsevier B.V. All rights reserved.