The intrinsic approach describing microscopic ionization equilibria is presented. This description massively reduces the number of parameters needed to characterize microequilibria. Particularly, by exploring molecular symmetries and group transferability, this approach is capable of resolving such equilibria even for rather complex molecules. Intrinsic constants are assigned to each ionizable group and interactions between these sites are introduced. These interactions involve pairs or triplets of sites. The strength of these interactions decreases rapidly with the distance between the sites. Once these parameters are known, one can obtain macroconstants, microconstants, microstate mole fractions, and overall or site-specific titration curves. These quantities provide insight into the protonation of the molecules in question. The knowledge of such properties is relevant for a wide range of phenomena, including receptor–ligand interactions, action of drugs, or geochemical processes.