Peptides are the means by which immune effector T cells recognize and defend against the foreign proteins of pathogens. T cell recognition of these molecules, however, is strictly dependent on peptide binding to the receptor-like molecules of the major histocompatibility complex (MHC) locus. The basic unit of recognition is a trimolecular complex consisting of the T cell antigen receptor, the MHC molecule, and the MHC-bound peptide ligand. The multistep process that culminates in MHC presentation of peptides to T cells begins in the last phases of protein catabolism. While the individual roles of many key molecules involved in peptide presentation have recently been defined, there still remain many questions regarding processing of proteins into MHC-bound peptides. This review summarizes the recent developments in peptide antigen processing for MHC molecules, with focus on how proteins are believed to be sampled and selected for degradation into peptides.