Pattern recognition receptors (PRR) of the innate immune system mediate the first line of defence against infections and cellular stress signals. The inflammasome complexes initiated by a subset of PRRs form a platform for activation of procaspase-1. Active caspase-1 cleaves gasdermin D leading to membrane pore formation and rapid lytic death, and also processes precursors of inflammatory cytokines IL-1b and IL-18. The central role of IL-1b in inflammatory pathology has led to great interest in inflammasome regulation. PRRs such as NLRP3 that responds to diverse cellular stresses, and AIM2 that responds to cytosolic DNA, initiate recruitment of the adapter molecule ASC. Within minutes, all the ASC in the cell can polymerise into a single “speck” via formation of pyrin domain (PYD) filaments, and condensation of these via caspase activation domain (CARD) interactions. ASC in turn recruits procaspase-1 via CARD-CARD interactions. We demonstrated that there is a more complex web of caspase activation by inflammasomes, and procaspase-8 is recruited to cap the ASC PYD filament. Its activation can lead to inflammasome-dependent apoptosis in cell types not expressing caspase-1. In current work we are closely examining the relative timing of events in inflammasome activation, in order to elucidate the essential structural features for caspase activation.