In chiral separation, capillary electrophoresis (CE) is a leading technique and, due to the absence of any stationary phase, it is an all-in-solution process, thus allowing accurate study of separation mechanisms. This review focuses on the leading role played by knowledge of solution equilibria for a deep understanding of the phenomena involved in the chiral-discrimination mechanisms at a molecular level in chiral ligand-exchange CE. Speciation diagrams have been accurately calculated on the basis of the stability-constant values reported in the literature for the evaluation of the species present in solution and their concentrations. This analytical approach turned out to be very useful in understanding electrophoretic behavior and should be used systematically to predict and to optimize chiral separations.