The determination of distillation column configurations that consume the least total energy is studied. The novel contributions of the proposed design methodology for finding global minimum energy column sequences presented in this article include: (1) the definition of a total stripping line distance function for any sequence, (2) a robust energy targeting strategy that provides a continuously differentiable description of column sequences, (3) the flexibility to use any phase equilibrium model, (4) the ability to find column sequences that contain non-pinched, minimum energy columns within a sequence, and (5) the ability to include heat integration. The proposed energy targeting approach, which is used in conjunction with the two-level design methodology of Amale & Lucia (2008b), is shown to be a reliable and effective tool for finding minimum energy distillation column sequences. A number of example problems are presented to show the efficacy of the proposed design methodology. (C) 2009 Elsevier Ltd. All rights reserved.