This work covers general multistage binary separations with application examples in cooling crystallization, evaporative crystallization and organic solvent nanoltration. Deterministic global optimization is applied to identify optimal congurations of multistage separation networks and study their sensitivity to parameter values. Superstructure optimization is conducted for countercurrent cascades and also for general superstructures to identify new multistage congurations. Results show substantially reduced separation eort for alternative congurations in large parameter regions, specically in regions where optimal countercurrent cascades have a low number of stages. General, simple design guidelines for multistage separation with a low number of stages are derived from rigorous global optimization by comparing results for dierent processes.