An overview is given of the theory and computational techniques for studying enzymatic reactions. Focus is on the identification of key features that lower the free energy of activation relative to the uncatalyzed reaction in water. It is emphasized that in order to achieve the required accuracy to understand catalysis, it is essential to parametrize and validate the potential energy functions against model reactions and specific hydrogen bonding interactions in the gas phase. The choice of the reaction coordinate for determining the free energy of activation to characterize the mechanism of enzymatic processes is outlined. Finally, several factors found to contribute to catalysis in specific enzymatic reactions by lowering the free energy of activation relative to that for the uncatalyzed process in aqueous solution are illustrated.