We rationalize the chemical reactivity and selectivity for a set of substituted cobalt phthalocyanines (CoPc-(X)(n)) in terms of the global and local HSAB (hard soft acid base) principle. Electron donating and electron withdrawing groups were used as substituents. At a global level, we analyze the reactivity in terms of the molecular hardness that present each of the species. At a local level, the graphical maps of the Fukui function for identifying the selectivity of the different sites in the substituted cobalt plithalocyanines are obtained. It is shown that the reaction site in a soft CoPc(X)(n) is associated to a maximum value in the Fukui function. In contrast to this, for a hard CoPc(X)(n) the Fukui function focus seem not to be the adequate criterion to identify the reaction site. The results obtained at the PM3(tm) semiempirical level lead to conclude that the interactions with the CoPc(X)(n) species will be governed by hard-hard and soft-soft interactions.