Substituent effects on cation-pi interactions have been quantified using a variety of Phi-X center dot center dot center dot M+ complexes where Phi, X, and M+ are the pi-system, substituent, and cation, respectively. The cation-pi interaction energy, EM+, showed a strong linear correlation with the molecular electrostatic potential (MESP) based measure of the substituent effect, Delta V-min (the difference between the MESP minimum (V-min) on the pi-region of a substituted system and the corresponding unsubstituted system). This linear relationship is EM+ = CM+(Delta V-min) + EM+' where CM+, is the reaction constant and EM+' is the cation-pi interaction energy of the unsubstituted complex. This relationship is similar to the Hammett equation and its first term yields the substituent contribution of the cation-pi interaction energy. Further, a linear correlation between CM+ and EM+' has been established, which facilitates the prediction of CM+ for unknown cations. Thus, a prediction of EM+ for any Phi-X center dot center dot center dot M+ complex is achieved by knowing the values of EM+' and Delta V-min. The generality of the equation is tested for a variety of cations (Li+, Na+, K+, Mg+, BeCl+, MgCl+, CaCl+, TiCl3+, CrCl2+, NiCl+, Cu+, ZnCl+, NH4+, CH3NH3+, N(CH3)(4)(+), C(NH2)(3)(+)), substituents (N(CH3)(2), NH2, OCH3, CH3, OH, H, SCH3, SH, CCH, F, Cl, COOH, CHO, CF3, CN, NO2), and a large number of pi-systems. The tested systems also include multiple substituted pi-systems, viz, ethylene, acetylene, hexa-1,3,5-triene, benzene, naphthalene, indole, pyrrole, phenylalanine, tryptophan, tyrosine, azulene, pyrene, [6]-cyclacene, and corannulene and found that E-M(+) follows the additivity of substituent effects. Further, the substituent effects on cationic sandwich complexes of the type C6H6 center dot center dot center dot M+center dot center dot center dot C6H5X have been assessed and found that EM+ can be predicted with 97.7% accuracy using the values of EM+' and Delta V-min. All the Phi-X center dot center dot center dot M+ systems showed good agreement between the calculated and predicted EM+' values, suggesting that the Delta V-min approach to substituent effect is accurate and useful for predicting the interactive behavior of substituted pi-systems with cations.