Purpose of Review <p>This review recognizes gout as an autoinflammatory disease rather than a solely metabolic condition. It provides an overview of autoinflammatory diseases, the NOD-, LRR, and pyrin domain-containing protein 3 (NLRP3) inflammasome, and how soluble and crystalline forms of uric acid (UA) act as inflammatory triggers, prompting NLRP3 inflammasome formation and activation. It also highlights the genetics associated with the autoinflammatory features of gout and discusses NLRP3 inflammasome-targeted treatments.</p> Recent Findings <p>Autoinflammatory diseases result from hyperactivity of the innate immune system, and the NLRP3 inflammasome complex, an innate immune sentinel and nonspecific sensor of cellular perturbation, is the initiator and key participant in gouty inflammation. Both the soluble and crystalline forms of UA act as inflammatory triggers, leading to the formation and activation of the NLRP3 inflammasome further promoting caspase 1-dependent release of the pro-inflammatory cytokines interleukin (IL)-1β and IL-18, as well as to gasdermin D-mediated pyroptotic cell death. Intracellular soluble UA also induces endothelial nitric oxide synthase dysfunction, oxidative stress, and inflammation. These mechanisms explain UA’s important role in promoting inflammatory pathways in patients.</p> Summary <p>Gout is now recognized as a disease rooted in innate immune dysregulation, with uric acid-driven activation of the NLRP3 inflammasome. Integrating the autoinflammatory perspective highlights the opportunities for developing targeted treatments. Emerging therapies focused on NLRP3 inhibition coupled with urate-lowering strategies may offer a better approach for managing gout flares.</p>