Recognition of infected or altered cells by CD8+ cytotoxic T lymphocytes is mediated by direct interaction of their T-cell receptor with peptides presented by MHC class I molecules. Peptides are transferred for assembly with newly synthesized MHC molecules by the transporters associated with antigen processing (TAP). Yet, a fraction of described epitopes are presented independently of TAP. Current belief is that most of them derive from membrane proteins, mostly from their signal sequences, and are processed by vesicular proteases. A thorough review of the published data may challenge some of these views.