We present joint theoretical and experimental results which provide evidence for the selectivity of VxOy+ clusters in reactions toward ethylene due to the charge and different oxidation states of vanadium for different cluster sizes. Density functional calculations were performed on the reactions between VxOy+ and ethylene, allowing us to identify the structure-reactivity relationship and to corroborate the experimental results obtained by Castleman and co-workers (Zemski, K. A.; Justes, D. R.; Castleman, A. W., Jr. J. Phys. Chem. A 2001, 105, 10237). The lowest-energy structures for the V2O2-6+ and V4O8-10+ clusters and the V2O3-6+-C2H4 and V4O10+-C2H4 complexes, as well as the energetics for reactions between ethylene and V2O4-6+ and V4O10+ are presented here. The oxygen transfer reaction pathway was determined to be the most energetically favorable one available to V2O5+ and V4O10+ via a radical-cation mechanism. The association and replacement reaction pathways were found to be the optimal channels for V2O4+ and V2O6+, respectively. These results are in agreement with the experimental results reported previously. Experiments were also conducted for the reactions between V2O5+ and ethylene to include an energetic analysis at increasing pressures. It was found that the addition of energy depleted the production Of V2O4+, confirming that a more involved reaction rather than a collisional process is responsible for the observed phenomenon. In this contribution we show that investigation of reactions involving gas-phase cationic vanadium oxide clusters with small hydrocarbons is suitable for the identification of reactive centers responsible for selectivity in heterogeneous catalysis.