The FAS (APO-1 or CD95) receptor and its ligand, FASL (CD95L), play crucial roles in the immune system, particularly in the regulation of lymphocyte homeostasis and the prevention of autoimmunity and tumor development. FASL-FAS signaling triggers apoptosis through the recruitment and activation of caspase-8 via the FADD adaptor protein. In certain cells, such as hepatocytes, FAS-induced apoptosis requires amplification through the proteolytic activation of BID, a pro-apoptotic member of the BCL-2 family. Several components of the FAS signaling machinery have also been implicated in non-apoptotic processes, including cellular activation, differentiation, and proliferation. The role of FASL-FAS signaling in normal and pathological killing of target cells, as well as its impact on lymphocyte homeostasis, is discussed. Studies using mutant mice and cell lines have revealed that FASL-FAS signaling is critical for the deletion of autoreactive T and B cells during immune responses, but not during their development in primary lymphoid organs. The generation of cell type-specific FAS knockout mice has provided insights into the specific functions of FAS in different cell types, highlighting its role in preventing lymphadenopathy and autoimmunity. Additionally, the non-apoptotic activities of components of the 'death receptor' signaling machinery, such as FADD and caspase-8, have been explored, with evidence suggesting that they also perform important functions in cell activation, proliferation, and differentiation.The FAS (APO-1 or CD95) receptor and its ligand, FASL (CD95L), play crucial roles in the immune system, particularly in the regulation of lymphocyte homeostasis and the prevention of autoimmunity and tumor development. FASL-FAS signaling triggers apoptosis through the recruitment and activation of caspase-8 via the FADD adaptor protein. In certain cells, such as hepatocytes, FAS-induced apoptosis requires amplification through the proteolytic activation of BID, a pro-apoptotic member of the BCL-2 family. Several components of the FAS signaling machinery have also been implicated in non-apoptotic processes, including cellular activation, differentiation, and proliferation. The role of FASL-FAS signaling in normal and pathological killing of target cells, as well as its impact on lymphocyte homeostasis, is discussed. Studies using mutant mice and cell lines have revealed that FASL-FAS signaling is critical for the deletion of autoreactive T and B cells during immune responses, but not during their development in primary lymphoid organs. The generation of cell type-specific FAS knockout mice has provided insights into the specific functions of FAS in different cell types, highlighting its role in preventing lymphadenopathy and autoimmunity. Additionally, the non-apoptotic activities of components of the 'death receptor' signaling machinery, such as FADD and caspase-8, have been explored, with evidence suggesting that they also perform important functions in cell activation, proliferation, and differentiation.