Infections with cytomegaloviruses are characterized by an intricate balance between the expression of immunomodulatory viral proteins and antiviral immune defence. For human cytomegalovirus (HCMV), several proteins have been described that interfere with the recognition of infected cells by CD8 T lymphocytes. Although the modes of action of these proteins have been elucidated on the molecular level, thus rendering them useful models to understand MHC class I peptide loading and transport, their role during viral infection has remained enigmatic. We exemplify here, how HCMV mutants can help to understand the importance of individual immunomodulatory proteins in the context of viral infection.