Phagocytosis leads to the destruction of many bacteria and the proteolytic degradation of bacterial antigens within phagolysosomes to produce immunogenic peptides that bind to Class II major histocompatibility (MHC) molecules within vacuolar compartments. On the other hand, Class I MHC molecules bind cytosol-derived peptides, including peptides from bacteria that escape the vacuolar system and penetrate into the cytosol. A recently described pathway may also allow the presentation of peptides from intravacuolar organisms by Class I MHC molecules in some cases. T cell recognition of peptide-MHC complexes then provides the primary basis for specific immunity to protein antigens of bacteria. This article will review the subcellular compartments and mechanisms involved in generating immunogenic peptides, the subcellular localization of MHC molecules that bind these peptides, and bacterial parameters that affect antigen processing.