Caspase-8 has dual functions: promoting apoptosis through the extrinsic pathway and maintaining cell survival during embryonic development and immune cell activation. This study investigates the role of caspase-8 in inhibiting RIPK3-dependent necrosis. Caspase-8-deficient mice are rescued by deleting Receptor Interacting Protein Kinase-3 (RIPK3), leading to a lymphoaccumulative disease similar to that seen in CD95 or CD95-ligand defects. Caspase-8 prevents RIPK3-dependent necrosis without inducing apoptosis by forming a proteolytically active complex with FLICE-Like Inhibitory Protein Long (FLIPL). The caspase-8-FLIPL complex is essential for this protective function. Non-cleavable caspase-8, which lacks the catalytic site, can rescue caspase-8-deficient mice without restoring apoptosis. FLIPL imparts catalytic activity to non-cleavable caspase-8, and both proteins are required to disrupt the stable association of FADD, RIPK1, and RIPK3, thereby preventing RIPK3-dependent necrosis. The study suggests that caspase-8's primary non-apoptotic function is to suppress RIPK3-dependent necrosis during development and immune cell proliferation.Caspase-8 has dual functions: promoting apoptosis through the extrinsic pathway and maintaining cell survival during embryonic development and immune cell activation. This study investigates the role of caspase-8 in inhibiting RIPK3-dependent necrosis. Caspase-8-deficient mice are rescued by deleting Receptor Interacting Protein Kinase-3 (RIPK3), leading to a lymphoaccumulative disease similar to that seen in CD95 or CD95-ligand defects. Caspase-8 prevents RIPK3-dependent necrosis without inducing apoptosis by forming a proteolytically active complex with FLICE-Like Inhibitory Protein Long (FLIPL). The caspase-8-FLIPL complex is essential for this protective function. Non-cleavable caspase-8, which lacks the catalytic site, can rescue caspase-8-deficient mice without restoring apoptosis. FLIPL imparts catalytic activity to non-cleavable caspase-8, and both proteins are required to disrupt the stable association of FADD, RIPK1, and RIPK3, thereby preventing RIPK3-dependent necrosis. The study suggests that caspase-8's primary non-apoptotic function is to suppress RIPK3-dependent necrosis during development and immune cell proliferation.