The SM8 quantum mechanical aqueous continuum solvation model is applied to a 17-molecule test set proposed by Nicholls et al. (J. Med. Chem. 2008, 51, 769) to predict free energies of solvation. With the M06-2X density functional, the 6-31G(d) basis set, and CM4M charge model, the root-mean-square error (RMSE) of SM8 is 1.08 kcal mol-1 for aqueous geometries and 1.14 kcal mol -1 for gas-phase geometries. These errors compare favorably with optimal explicit and continuum models reported by Nicholls et al., having RMSEs of 1.33 and 1.87 kcal mol-1, respectively. Other models examined by these workers had RMSEs of 1.5-2.6 kcal mol-1. We also explore the use of other density functional and charge models with SM8 and the RMSE increases to 1.21 kcal mol-1 for mPW1/CM4 with gas-phase geometries, to 1.50 kcal mol-1 for M06-2X/CM4 with gas-phase geometries, and to 1.27-1.64 kcal mol-1 with three different models at B3LYP gas-phase geometries.