Molecular crystals have been studied using two new forms of the cluster approach: an extended point charge (PCX) and an extended supermolecule (SMX) model. These models extend, using a hybrid quantum mechanical/molecular mechanical (QM/MM) approach, that part of the molecular environment that was previously described by point charges in, respectively, the point charge (PC) and supermolecule (SM) models. After interfacing the ab initio program BRABO with the molecular mechanics program CHARMM. the PCX and SMX models have been tested on formamide oxime, a-glycine, and the yellow form of dimethyl 3,6-dichloro-2,5-dihydroxyterephthalate. PCX results are in notably better agreement with experimental results than PC results and are shown to be a viable alternative to SM calculations. For alpha-glycine, the SMX model improves results over the SM model. For dimethyl 3,6-dichloro-2,5-dihydroxyterephthalate, it was shown that the SMX model can give SM-quality results when fewer neighbors are included in the wave function, thereby reducing the computation time significantly. As a second part of this study, the PCX model was applied to the geometry optimization of the four polymorphs of 2-(2-methyl-3-chloroanilino) nicotinic acid. In contrast to a previous study using the PC model, the newly developed PCX model introduced in this study allowed full geometry optimization of all polymorphs.