Fas is a death receptor belonging to the TNFR superfamily and induces cell apoptosis by both activating a caspase cascade and altering mitochondria. In the immune system, Fas is involved in the switching-off of the immune responses and cell mediated cytotoxicity. In humans, genetic defects decreasing Fas function cause the Autoimmune Lymphoproliferative Syndrome (ALPS) where autoimmunities are associated with accumulation of polyclonal lymphocytes in the secondary lymphoid tissues and expansion of T cells lacking both CD4 and CD8 (DN cells). Expansion of DN cells is absent in an ALPS variant, named Dianzani's Autoimmune Lymphoproliferative Disease (DALD). The observation that DALD patients' families display increased frequency of autoimmune diseases different from ALPS suggests that defects of Fas function may also play a role in development of "common" autoimmune diseases. This possibility is supported by detection of defective Fas function in substantial proportions of patients with the multiple autoimmune syndrome or aggressive forms of type 1 diabetes or multiple sclerosis. This article reviews data suggesting that development of autoimmune/lymphoproliferative patterns may involve several alterations hitting the Fas system, but might also involve alterations in other systems contributing to the switching-off or proliferation of lymphocytes.