The binding of bound peptide ligands to major histocompatibility complex (MHC) molecules plays a key role in the activation of normal immune responses and is an intricate theoretical problem that remains unsolved. Geometric and energetic complementarities between an MHC molecule and its corresponding bound peptide ligand are critical in determining the stability of the complex. In this context, the introduction of structural information can greatly facilitate our understanding of how well a peptide ligand can associate with a particular MHC molecule. This chapter introduces the use of structural models as a predictive method to determine whether a peptide sequence can bind to a specific MHC allele