Cell-mediated immune responses are important for the control of HIV replication in vivo. Cytotoxic CD8+ T cells (CTL) recognize and kill HIV-infected cells which display MHC class-I proteins. In addition to the recognition and killing of infected cells, CD8+T cells can interfere with stages of the HIV life-cycle. Chemokines produced by CD8+ T cells bind to their seven-transmembrane G protein-coupled receptors resulting in a block in the entry of HIV into macrophages and T cells. In addition, activated CD8+ T cells produce factors which strongly modulate HIV at the level of transcription. This review will focus primarily on the current knowledge of the multifactorial functions of CD8+ T cells in HIV infection. An understanding of the mechanisms involved in the CD8-mediated control of transcription may identify other factors with potential value in the treatment of HIV infection.