Inflammatory caspases play a central role in innate immunity by responding to cytosolic signals and initiating a twofold response. First, caspase‐1 induces the activation and secretion of the two prominent pro‐inflammatory cytokines, interleukin‐1β (IL‐1β) and IL‐18. Second, either caspase‐1 or caspase‐11 can trigger a form of lytic, programmed cell death called pyroptosis. Pyroptosis operates to remove the replication niche of intracellular pathogens, making them susceptible to phagocytosis and killing by a secondary phagocyte. However, aberrant, systemic activation of pyroptosis in vivo may contribute to sepsis. Emphasizing the efficiency of inflammasome detection of microbial infections, many pathogens have evolved to avoid or subvert pyroptosis. This review focuses on molecular and morphological characteristics of pyroptosis and the individual inflammasomes and their contribution to defense against infection in mice and humans.