The availability of genome sequences for many organisms enabled the reconstruction of several genome-scale metabolic network models. Currently, significant efforts are put into the automated reconstruction of such models. For this, several computational tools have been developed that particularly assist in identifying and compiling the organism-specific lists of metabolic reactions. In contrast, the last step of the model reconstruction process, which is the definition of the thermodynamic constraints in terms of reaction directionalities, still needs to be done manually. No computational method exists that allows for an automated and systematic assignment of reaction directions in genome-scale models.