The recently developed Charge Model 5 (CM5) is tested for its utility in condensed-phase simulations. The CM5 approach, which derives partial atomic charges from Hirshfeld population analyses, provides excellent results for gas-phase dipole moments and is applicable to all elements of the periodic table. Herein, the adequacy of scaled CM5 charges for use in modeling aqueous solutions has been evaluated by computing free energies of hydration (ΔGhyd) for 42 neutral organic molecules via Monte Carlo statistical mechanics. An optimal scaling factor for the CM5 charges was determined to be 1.27, resulting in a mean unsigned error (MUE) of 1.1 kcal/mol for the free energies of hydration. Testing for an additional 20 molecules gave an MUE of 1.3 kcal/mol. The high precision of the results is confirmed by free energy calculations using both sequential perturbations and complete molecular annihilation. Performance for specific functional groups is discussed; sulfur-containing molecules yield the largest errors. In addition, the scaling factor of 1.27 is shown to be appropriate for CM5 charges derived from a variety of density functional methods and basis sets. Though the average errors from the 1.27*CM5 results are only slightly lower than those using 1.14*CM1A charges, the broader applicability and easier access to CM5 charges via the Gaussian program are additional attractive features. The 1.27*CM5 charge model can be used for an enormous variety of applications in conjunction with many fixed-charge force fields and molecular modeling programs.