The generalized Born/surface area (GB/SA) model of Still and co-workers was originally developed using partial atomic charges for organic molecules and ions from the OPLS united-atom force field. An efficient implementation of the GB/SA approach with the OPLS-AA (all-atom) force field is described here. Migration to the OPLS-AA model allows much broader application, and it also yields improved accuracy in predicting free energies of hydration. For 75 diverse, neutral organic molecules, the mean unsigned error is 0.6 kcal/mol with the OPLS-AA GB/SA model. Furthermore, effects of hydration on conformational equilibria are shown to be well represented, and results for free energies of hydration of a wide variety of ions are also in close accord with experimental data. As an even more general alternative, the use of partial charges from the CM1A procedure of Cramer, Truhlar, and co-workers has been tested on more than 400 organic molecules and ions. OPLS-AA force field parameters are also reported for primary alkyl halides, halobenzenes, and numerous ions.