The part played by CD8 lymphocytes in the pathogenesis of human immunodeficiency virus infection (HIV) is much disputed and the relevant issue of the controversy ranges as to whether the functional activity of these cells is beneficial or detrimental to the host. Even though CD8 cells could efficiently suppress HIV replication through both major histocompatibility complex (MHC)-restricted cytotoxic killing of infected cells, particularly during primary infection, and HIV-suppressing soluble factors, there is evidence that tissue-infiltrating CD8 lymphocytes mediate injury in several organs of HIV-infected subjects. Furthermore, CD8 lymphocytes could contribute to the destruction of CD4 cells in vivo. Of note, the virus has the capability to escape the recognition by cytotoxic CD8 cells and the cytotoxic activity of CD8 cells and their counts decline with evolving HIV infection. Several mechanisms are proposed to explain this latter finding, including the direct in vivo infection of CD8 cells by the virus. It is likely that early during the course of HIV infection when viral loads are generally low an efficient CD8 cell response can control HIV replication whereas in subjects with evolving disease, who have very high viral loads, CD8 lymphocytes remove essential components of the immune response and mediate tissue injury.