We briefly review current evidence which indicates that major histocompatibility complex (MHC)-restricted, virus-specific cytotoxic T cells may be of immunological importance in protection from infection with immunodeficiency virus or with protection from disease progression which would finally result in acquired immunodeficiency syndrome (AIDS) and death. We suggest that prophylactic vaccines should elicit cytotoxic T lymphocyte (CTL) activity in naive individuals. Further, immunotherapy in infected individuals could be aimed at ensuring that levels of virus-specific CTL are kept high, broadening and redirecting their specificity towards conserved parts of the viral genome.