Molecular recognition plays a vital role in a wide variety of biochemical transformations. Of particular interest to chemists, biochemists, and biologists is the process by which enzymes recognize and bind substrates in the catalytic process. The relationship of peptide structure to properties and biological activity is the most important aspect of studies of molecular recognition. Enzyme binding studies are complicated because of the numerous variables in the binding process, which include the flexibility of substrates and inhibitors in solution, the paucity of enzyme structural information, and the dynamic nature of the enzyme/substrate complex structure. Recent advances in X-ray crystallography and molecular modeling have allowed researchers to determine the coordinates of many bound inhibitor/enzyme complexes and analyze the bound conformation of inhibitors. The HIV-1 protease has been the subject of several recent X-ray crystallographic studies, so the general topography of bound HIV-1 protease inhibitors is well established. In addition, numerous HIV protease inhibitor and substrate binding studies have established the enzyme's ligand preferences at important binding subsites.