The recently developed frozen density functional theory (FDFT) is extended to ab initio free energy calculations of chemical reactions in solution. This method treats the solute−solvent system as a supermolecule but constrains the electron density of the solvent molecules. Unlike hybrid quantum mechanical/molecular mechanics techniques, FDFT represents the solvent quantum mechanically. The quality of the solute−solvent interaction potential is examined by generating clusters of a reacting system and several solvent molecules and comparing the supermolecule DFT energies to the corresponding FDFT energies. The FDFT potential surfaces for solute−solvent systems provide a good approximation of the supermolecule DFT surfaces and require, in some cases, several orders of magnitude less computation time (in particular if one treats many solvent molecules quantum mechanically). The ab initio free energy surface for the F^- + HF → FH + F^- proton transfer reaction in solution is calculated using the corresponding “classical� empirical valence bond (EVB) potential surface as a reference potential. The encouraging results indicate that FDFT can be used to study chemical reactions in solution, capturing the quantum mechanical aspects of the solvent, which is not possible using hybrid quantum mechanical/molecular mechanics approaches. Furthermore, the use of EVB as a reference potential is found to be an extremely effective way of obtaining ab initio free energies for chemical processes in solution or in clusters.