Interactions of metal cations with nucleic acids are substantially affected by polarization and charge transfer effects. These contributions are not included in the presently available molecular modeling force fields and often not considered in structural biology studies where the assumption is that the metal cations can be described by assuming their charge and radius. The metal cations may substantially affect the strength of base pairing, base stacking, induce proton shift processes (tautomerism, protonation, deprotonation), etc. To properly analyze the metal cation interactions, one needs to characterize the balance of long-range electrostatic and nonelectrostatic effects and their expression in different environments. Non-electrostatic contributions decisively affect the selectivity of metal cations with respect to different binding sites in nucleic acids, such as the zinc vs. magnesium difference, balance of solute ? cation and solvent ? cation interactions, and others. Recent results obtained by reliable molecular orbital calculations are discussed.