Different column configurations in a distillation network can achieve the same ultimate products, with different amounts of energy to do so. Only recently. methods have been discovered for the systematic generation and evaluation of all possible complex column configurations for the separation of multicomponent mixtures. However, there is a lack of robust methods for the globally optimal design of complex column sequences. This presentation reviews recent advances to tackle the challenges of synthesizing complex column networks with computer-aided design algorithms. An automatic procedure to generate optimal column sequences based on a thermodynamic problem transformation called temperature collocation is discussed and its current capabilities and limitations illustrations with the help of two realistic case studies. (C) 2009 Elsevier Ltd. All rights reserved.