Polyoxometalates (POMs) are inorganic entities featuring extensive and sometimes unusual redox properties. In this work, several experimental techniques as well as density functional theory (DFT) calculations have been applied to identify and assess the relevance of factors influencing the redox potentials of POMs. First, the position of the Mo substituent atom in the Wells-Dawson structure, alpha(1)- or alpha(2)-P2W17Mo, determines the potential of the first 1e(-) reduction wave. For P2W18-xMox systems containing more than one Mo atom, reduction takes place at successively more positive potentials. We attribute this fact to the higher electron delocalization when some Mo oxidizing atoms are connected. After having analyzed the experimental and theoretical data for the monosubstituted alpha(1)- and alpha(2)-P2W17Mo anions, some relevant facts arise that may help to rationalize the redox behavior of POMs in general. Three aspects concern the stability of systems: (i) the favorable electron delocalization, (ii) the unfavorable e(-)-e(-) electrostatic repulsion, and (iii) the favorable electron pairing. They explain trends such as the second reduction wave occurring at more positive potentials in alpha(1)- than in alpha(2)-P2W17Mo, and also the third electron reduction taking place at a less negative potential in the case of alpha(2); reversing the observed behavior for the first and the second waves. In P2W17V derivatives, the nature of the first "d" electron is more localized because of the stronger oxidant character of V-v. Thus, the reduction potentials as well as the computed reduction energies (REs) for the second reduction of either isomer are closer to each other than in Mo-substituted POMs. This may be explained by the lack of electron delocalization in monoreduced P2W17VIV systems.