The article provides an overview of the regulation of inflammasome activation, highlighting its roles in host defense against pathogens and the development of various diseases. Inflammasomes are formed by the assembly of nucleotide-binding domain and leucine-rich repeat receptors (NLRs) or absent in melanoma 2-like receptors (ALRs) upon sensing pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs). The assembly of inflammasomes typically involves the recruitment of caspase-1, often through the adapter protein apoptosis-associated speck-like protein containing a CARD (ASC), which facilitates the proteolytic cleavage of pro-interleukin-1β (pro-IL-1β) and pro-IL-18, leading to pyroptosis. Recent studies have also identified other components, such as caspase-8, caspase-11, IL-1R-associated kinases (IRAK), and receptor-interacting protein (RIP) kinases, that contribute to inflammasome functions. Post-translational modifications, including ubiquitination, deubiquitination, phosphorylation, and degradation, play crucial roles in controlling inflammasome activities. Genetic mutations in NLRP1, NLRP3, NLRC4, and AIM2 have been linked to autoinflammatory diseases, enterocolitis, and cancer. The article discusses the latest advancements in inflammasome research, emphasizing the regulation of inflammasome signaling in health and disease, and highlights the potential for developing immunotherapies targeting inflammasome components to combat infectious and inflammatory diseases.The article provides an overview of the regulation of inflammasome activation, highlighting its roles in host defense against pathogens and the development of various diseases. Inflammasomes are formed by the assembly of nucleotide-binding domain and leucine-rich repeat receptors (NLRs) or absent in melanoma 2-like receptors (ALRs) upon sensing pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs). The assembly of inflammasomes typically involves the recruitment of caspase-1, often through the adapter protein apoptosis-associated speck-like protein containing a CARD (ASC), which facilitates the proteolytic cleavage of pro-interleukin-1β (pro-IL-1β) and pro-IL-18, leading to pyroptosis. Recent studies have also identified other components, such as caspase-8, caspase-11, IL-1R-associated kinases (IRAK), and receptor-interacting protein (RIP) kinases, that contribute to inflammasome functions. Post-translational modifications, including ubiquitination, deubiquitination, phosphorylation, and degradation, play crucial roles in controlling inflammasome activities. Genetic mutations in NLRP1, NLRP3, NLRC4, and AIM2 have been linked to autoinflammatory diseases, enterocolitis, and cancer. The article discusses the latest advancements in inflammasome research, emphasizing the regulation of inflammasome signaling in health and disease, and highlights the potential for developing immunotherapies targeting inflammasome components to combat infectious and inflammatory diseases.