The various contributions to binding energies for cytochrome P450 enzyme-substrate interactions are discussed in the light of intermolecular forces of attraction in biological systems. These energies include: electrostatic, van der Waals, hydrogen bond, π-π stacking and desolvation processes. These individual components can be used to estimate the binding energies of P450 substrates, and the example of camphor in CYP101 is employed to demonstrate the particular merits of these approaches. The various methods of calculating desolvation energies are demonstrated for camphor binding to CYP101, together with estimation of the hydrogen bond energy associated with this process as they are thought to be the major contributions. The binding of warfarin to CYP2C9 is also discussed and evaluated in the light of the estimations for camphor binding to CYP101, thus indicating a degree of comparison between examples of bacterial and human P450-substrate interactions. The various force fields (Amber, Tripos and AutoDock) employed in energy calculations are also compared, together with typical values for the several individual components to the overall binding energy.