An effective extractive distillation process depends on the choice of the extractive agent. in this contribution, heuristic rules for entrainer selection and the design of entrainers through computer-aided molecular design are reviewed. The potential of the generated alternatives is then evaluated by their selectivity at infinite dilution and by the rectification body method (RBM). it is shown that a screening based on selectivity alone is not sufficient and could possibly lead to an unfavorable entrainer choice. The minimum entrainer flowrate and the minimum energy demand, calculated from the RBM, allow a more comprehensive evaluation of different entrainer alternatives. In a third step a rigorous mixed-integer optimization of the entire extractive flowsheet for the remaining entrainer candidates is executed to fix the remaining design degrees of freedom and to determine the best entrainer. Since a number of alternative entrainers have already been eliminated, only a few optimizations are necessary. These steps form a framework which facilitates the systematic generation and evaluation of entrainer alternatives. The suggested synthesis framework is illustrated with a case study where acetone and methanol are to be separated. (C) 2008 The Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.