Significant progress has been made in the use of molecular simulation (Monte Carlo and molecular dynamics) to predict octanol/water partition coefficients . In these efforts, the partition coefficient may be predicted with knowledge only of the structure of the solute. Moreover, these methods simultaneously may be used to understand the underlying molecular-level details. In general, the octanol/water partition coefficient is computed as the difference in solvation free energy in pure water and 1-octanol via eq. 3. While this has resulted in many accurate predictions, it physically is not in agreement with the experimental measurements. Specifically, the experimental measurements involve water-saturated 1-octanol. And following Tse and Sandler we know that ∆ G solv 1,o * = ∆ G solv 1,o . Previous work has acknowledged this and attempted to model water-saturated 1-octanol using the experimental mutual solubility. However, it has been found that the mutual solubility predicted with common molecular models differ from experiment. If a simulation were performed at experimental conditions which corresponds to a mutual solubility greater than that predicted by the model, it would correspond to a metastable system. While the sys-tem sizes and timescales are relatively small so that phase separation would not be observed, it would nonetheless correspond to a metastable system.