Regulated cell death is critical in multicellular organisms for development, protection against disease and for repair and renewal of tissues. The major forms of regulated cell death are apoptosis, which allows for discreet disposal of dying cells, and necroptosis, where cells burst open, sparking an immediate inflammatory response. Although cell death is critically important in diseases such as cancer and viral infections, how cells decide which form to undertake is poorly understood. We recently discovered that the important mammalian cell-death protein caspase-8 is regulated by a small‑molecule oxidant, called hypothiocyanous acid, produced by the immune system.1 This oxidant causes cells to switch to necroptosis and inflammatory cell death. Unexpectedly, we find that oxidation causes caspase‑8 to switch to an aggregated state, both in cellular models and in vitro. Caspase-8 aggregates show features consistent with amyloid fibrils—a protein conformation usually associated with disease but increasingly found to have regulatory functions. We find that the thiol-specific oxidant causes formation of disulfide-bond between specific cysteines, triggering the transition into amyloid. We are unravelling the mechanism of this structural and functional switch at both the molecular and cellular levels. This work will establish a novel regulatory mechanism in cell-fate decision making which may open avenues for future disease interventions.