Specific immune responses are critically dependent on protein degradation products in the form of peptides. These peptides are presented by major histocompatibility complexes (MHCs), and recognition of MHC-peptide complexes by the immune system determines successful pathogen elimination, transplant rejection, autoimmunity or death. Here we review the immune response from the peptide's perspective and discuss the fate of peptides in cells before presentation by MHC complexes. We then discuss how peptides are altered post-translationally to yield immune responses and how peptides can be engineered to achieve strong immune responses following vaccination. Although peptides are simple from a chemical perspective, they are complex in their immunological consequences.