Inflammasomes are protein complexes assembled upon recognition of infection or cellular stress signals, leading to processing of proinflammatory cytokines and cell death. Although well known as platforms for activation of procaspase-1, leading to rapid lytic cell death termed pyroptosis, we have recently shown that NLRP3 and AIM2 inflammasomes can also initiate caspase-8-dependent apoptosis. Viral or bacterial cytosolic dsDNA is recognised by AIM2, whilst NLRP3 is induced to oligomerise in response to many stimuli, including extracellular ATP and the bacterial ionophore nigericin. Both these initiators induce oligomerisation of the adapter protein ASC which in turn, recruits procaspases. Apoptosis and pyroptosis are initiated simultaneously by inflammasome activation. The balance between apoptosis and pyroptosis depends on the strength of stimulus; apoptosis occurred at lower stimuli concentrations, while pyroptosis had a higher threshold for initiation. Gene knockdown showed that caspase-8 is the apical caspase in the inflammasome-dependent apoptotic pathways. Procaspase-8 co-localises with ASC inflammasome “specks” in cells, and binds directly to ASC. We have shown a novel heterotypic death domain interaction between ASC pyrin domain and the tandem death effector domains (DED) of procaspase-8. Caspase-8 activation is thus an integral part of the inflammasome response and this extends the relevance of inflammasome-mediated defence to cells which don’t normally express caspase-1. Activation of multiple death pathways may be an evolutionary response to pathogens attempting to subvert cell death.