Immune processes are tightly regulated to ensure protection against pathogens is balanced with immune-mediated pathology. The inflammasome is a signaling complex essential for the innate immune response elicited by pathogens and danger-associated signals. The primary function of this platform is to enable the activation of the zymogen proteases, caspase-1 and 11. Active caspase-1 enables the maturation of pro-inflammatory cytokines (IL-1β and IL-18) and both caspase-1 and -11 execute an inflammatory cell death program, pyroptosis.  Despite being central to key innate immune processes and associated pathologies, mechanisms of inflammatory caspase activation and deactivation remains poorly characterized. Here we use biochemical, cell biology and genetic approaches to define caspase activation requirements, and mechanisms controlling the duration of caspase activity. Our novel regulatory mechanisms give insight into temporal co-ordination of the immune response, and suggests new strategies for targeting inflammatory caspases in inflammatory disease.