Defects in multiple molecules within the Fas apoptotic pathway may result in autoimmune lymphoproliferative syndrome and, despite recent advances, a number of patients remain with unidentified genetic defects. There is also clear need for improved understanding of mechanisms underlying the development of autoimmunity in this disorder and to provide early evidence for development of malignancy. This syndrome is the first human disorder linked to a germline defect in lymphocyte apoptosis and it continues to be an area of productive research and new information regarding this process of lymphocyte homeostasis and its role in human disease.