Inflammasomes are key signaling platforms that detect pathogenic microorganisms and sterile stressors, activating pro-inflammatory cytokines IL-1β and IL-18. This review discusses the complex regulatory mechanisms that ensure a balanced but effective inflammasome-mediated immune response. It highlights similarities between inflammasomes and apoptosomes, another molecular signaling platform monitoring cellular health. The review covers extracellular and intracellular control mechanisms, including ion fluxes, free radicals, and autophagy. It also explores the role of co-receptors and cofactors in inflammasome activation, the differential requirements for various NLRP3 activators, and non-inflammasome processing of IL-1β. Additionally, it examines cell-extrinsic and cell-intrinsic regulation, including the influence of ion concentrations, redox state, and autophagy. The review concludes by discussing future perspectives and the potential for developing novel therapies targeting specific inflammasomes to treat inflammatory diseases.Inflammasomes are key signaling platforms that detect pathogenic microorganisms and sterile stressors, activating pro-inflammatory cytokines IL-1β and IL-18. This review discusses the complex regulatory mechanisms that ensure a balanced but effective inflammasome-mediated immune response. It highlights similarities between inflammasomes and apoptosomes, another molecular signaling platform monitoring cellular health. The review covers extracellular and intracellular control mechanisms, including ion fluxes, free radicals, and autophagy. It also explores the role of co-receptors and cofactors in inflammasome activation, the differential requirements for various NLRP3 activators, and non-inflammasome processing of IL-1β. Additionally, it examines cell-extrinsic and cell-intrinsic regulation, including the influence of ion concentrations, redox state, and autophagy. The review concludes by discussing future perspectives and the potential for developing novel therapies targeting specific inflammasomes to treat inflammatory diseases.