Human immunodeficiency virus disease involves progressive destruction of host immunity leading to opportunistic infections and increased rates for malignancies. Quantitative depletion of immune cell subsets and accruing defects in cell effector functions are together responsible for immunodeficiency The broad impact of HIV reflects a similarly broad spectrum of affected cells including subsets that do not express viral receptors or support viral replication. Indirect cell killing, the destruction of uninfected cells, is one important mechanism due partly to activation of the Fas/FasL system for cell death. This death-signaling pathway is induced during HIV disease and contributes significantly to viral pathogenesis and disease.