Caspase-1 is an integral regulator of the innate immune system. Its core functions are the processing and secretion of the proinflammatory cytokines interleukin 1β (IL-1 beta) and IL-18 and the initiation of proinflammatory cell death, which is referred to as pyroptosis. Activation of caspase-1 plays a pivotal role during immune defense mechanisms against infections by the innate immune system. Dysregulated activation of caspase-1 has been recognized to be involved in the pathophysiology of a constantly increasing number of inflammatory diseases. This article gives an overview of the regulation and function of caspase-1 and its involvement in monogenic, polygenic and/or polyetiological rheumatic diseases.