The article reviews the signaling pathways initiated by the CD95 (APO-1/Fas) death receptor, which has been a paradigm for death receptor family signaling. CD95, a member of the tumor necrosis factor (TNF) superfamily, is characterized by an 80 amino acid death domain in its cytoplasmic tail, essential for recruiting signaling components upon activation. The complex of proteins that forms upon triggering of CD95 is called the death-inducing signaling complex (DISC), which consists of an adaptor protein and initiator caspases and is crucial for inducing apoptosis. The review discusses recent developments in the regulation of DISC formation and activity, including the involvement of various proteins such as FADD, caspase-8, c-FLIP, Daxx, FAP-1, FLASH, RIP, FAF1, and DAP3. It also explores the role of c-FLIP in both activating and inhibiting caspase-8, and the formation of two different CD95 apoptosis cell types, Type I and Type II, based on the quantity of caspase-8 produced at the DISC. Additionally, the article covers ligand-independent DISC formation, CD95 clustering and internalization, and the role of CD95 in costimulation of T cells. The conclusion emphasizes the importance of understanding the complex death-signaling pathways for applying molecular intervention strategies in dysregulated death processes.The article reviews the signaling pathways initiated by the CD95 (APO-1/Fas) death receptor, which has been a paradigm for death receptor family signaling. CD95, a member of the tumor necrosis factor (TNF) superfamily, is characterized by an 80 amino acid death domain in its cytoplasmic tail, essential for recruiting signaling components upon activation. The complex of proteins that forms upon triggering of CD95 is called the death-inducing signaling complex (DISC), which consists of an adaptor protein and initiator caspases and is crucial for inducing apoptosis. The review discusses recent developments in the regulation of DISC formation and activity, including the involvement of various proteins such as FADD, caspase-8, c-FLIP, Daxx, FAP-1, FLASH, RIP, FAF1, and DAP3. It also explores the role of c-FLIP in both activating and inhibiting caspase-8, and the formation of two different CD95 apoptosis cell types, Type I and Type II, based on the quantity of caspase-8 produced at the DISC. Additionally, the article covers ligand-independent DISC formation, CD95 clustering and internalization, and the role of CD95 in costimulation of T cells. The conclusion emphasizes the importance of understanding the complex death-signaling pathways for applying molecular intervention strategies in dysregulated death processes.