The chemical groups undergoing protonation or deprotonation in solution are described by the acid dissociation constant value, the key parameter for physicochemical characterization of biologically- and pharmacologically-important compounds. Capillary electrophoresis (CE) proved to be suitable technique for its determination: it enables automated and accurate measurements even for minute amount of sample, does not require the information about concentration, and handle both the impure and complex samples. In this review, a number of contributions reporting on the application of CE in pKa prediction has been summarized and critically discussed. The reader will find herein the brief introduction of theory, summary of all works published in the last decade, considerations on the most important innovations and achievements, and the discussion of pKa-related issues as e.g. the role of pKa-shifts in the chiral separation mechanism or the elucidation of migration order reversals observed during CE-mediated separations.