The NALP3-inflammasome is a protein complex that stimulates caspase-1 activation to promote the processing and secretion of proinflammatory cytokines. Recent work indicates that the NALP3-inflammasome can be activated by endogenous “danger signals” as well as compounds associated with pathogens (Kanneganti et al., 2006, Mariathasan et al., 2006, Martinon et al., 2006, Sutterwala et al., 2006). Here, we discuss new insights into the regulation of caspase-1 activity in the inflammatory response.