Inflammasomes are key inflammatory signaling platforms that detect microbial substances, sterile environmental insults, and molecules derived from host cells. Activation of the inflammasome promotes caspase-1-mediated secretion of proinflammatory cytokines interleukin (IL)-1β and IL-18 and pyroptosis. Recent developments in this field demonstrate the crucial role of the inflammasome in a wide range of disease models. Although inflammasomes are a crucial part of host defense mechanisms against pathogens, the exuberant immune response resulting from inflammasome activation also contributes to the development of various diseases. As ongoing studies further elucidate the regulation and function of the inflammasome, more evidence has emerged that the inflammasome appears to play a pivotal role in the development of multiple inflammatory diseases. Here, we discuss recent insights into how inflammasomes are regulated to activate caspase-1 and implicated in human diseases. We also review the contributions of the inflammasome to pulmonary diseases.