Inflammasomes are multiprotein signalling platforms that activate the highly pro-inflammatory cytokines interleukin-1β (IL-1β) and IL-18 and induce cell death in response to pathogens and sterile stressors. This Review provides a comprehensive overview of our rapidly evolving understanding of the regulatory mechanisms that control the activation of distinct inflammasome components, as well as the non-canonical processing of IL-1β. Inflammasomes are key signalling platforms that detect pathogenic microorganisms and sterile stressors, and that activate the highly pro-inflammatory cytokines interleukin-1β (IL-1β) and IL-18. In this Review, we discuss the complex regulatory mechanisms that facilitate a balanced but effective inflammasome-mediated immune response, and we highlight the similarities to another molecular signalling platform — the apoptosome — that monitors cellular health. Extracellular regulatory mechanisms are discussed, as well as the intracellular control of inflammasome assembly, for example, via ion fluxes, free radicals and autophagy.