Considered a promising alternative for modeling large molecules of biochemical interest, the fragment molecular orbital method (FMO) shows great promise when applied to any number of biochemical problems, especially in drug design, protein-ligand binding, enzyme reactivity, and light-driven processes. This handbook, written by the inventors of the process, makes FMO accessible. The authors present the necessary foundation material in a way that the general scientist will understand and demonstrate applications to biochemical studies that emphasize practical aspects of performing actual simulations. The text pays some attention to FMO-enabled software. An attached CD-ROM will allow scientists to perform calculations.