Theoretical calculation using density functional B3LYP correlation-exchange is employed to study the structure of different sizes of the VAPO-5 clusters. The results indicate that the substitution of either the phosphorus site or the aluminum site of the aluminophosphate-5 framework with vanadium is generally not feasible. The calculated structures are comparable with those from the in-situ X-ray absorption (XANES and EXAFS) of the V K-edge. The isolated vanadium was found to exist as a mono-ore (V4+ = O)(O-f)(4) species for reduced, dehydrated VAPO-5 and as a di-oxo V5+O4 species for calcined, dehydrated VAPO-5. The coordination geometry of the mono-ore V4+ species is sensitive to the presence of water molecules, and the water molecules may exchange with the framework oxygens that are coordinated to the V4+ center.