The ability of the effective fragment potential (EFP) method, a quantum mechanical/molecular mechanical (QM/MM) approach, to describe the hydration of five simple anions (OH-, F-, SH-, Cl-, and Br-) by one to six water molecules was investigated. The results were compared with experimental data and ab initio calculations: Hartree-Fock (HF) and second-order Moller-Plesset (MP2). With the exception of the addition of the first water molecule, the EFP method was able to reproduce both the experimental and HF differential enthalpies of hydration. None of the three levels of theory reliably reproduced the experimental total enthalpies of hydration, and the EFP and HF results were found to be in poor agreement. The charge-transfer/exchange-repulsion component of the model appears to be inadequate in describing systems exhibiting large amounts of charge transfer (e.g., the OH- and F- systems). Two model chemistries based upon the EFP method were also examined. While the use of HF and MP2 single-point energy calculations at EFP-optimized geometries offered little improvement over the results obtained at the EFP level, the use of effective fragment potentials to model the second hydration shell of the larger anion-water clusters proved very successful. This latter result suggests that the method may be useful in the description of much larger hydrated systems.