Polyoxometalates (POMs) have been applied as catalysts because their chemical properties can be tuned via cluster structure design. The negativity of the surface O atoms of POMs is believed to be an important chemical property for base catalytic applications. Moreover, pentavalent metals (M5+) such as group 5 elements (V, Nb, Ta) are the most promising constituent metals for POMs as base catalysts according to the trade-off between the basicity and the stability of the clusters. In this chapter, the possibility of using group 5 POMs for base catalytic applications is demonstrated theoretically and experimentally. Density functional theory calculations of various POMs were conducted to evaluate the basicity of the surface O atoms. Based on these theoretical predictions, [Nb10O28]6− was chosen as a representative group 5 POM and was applied as homogeneous catalyst for aldol-type condensation reactions such as the Knoevenagel and Claisen–Schmidt condensation reactions. [Nb10O28]6− was found to act as a Brønsted base catalyst whose strength is comparable to that of superbases. This result opens up the possibility of applying group 5 POMs as base catalysts.