IL-18 is mainly a proinflammatory cytokine for host defense against pathogens, but when out of balance with its dyad’s partner, IL-18 is associated with various autoimmune and inflammatory disorders, such as adult-onset Still’s disease, hemophagocytic syndrome, macrophage activation syndrome, fulminant hepatitis, lupus erythematosus, inflammatory bowel diseases, atopic dermatitis, psoriasis, and more. This evidence concerns the gene IL18 and adult-onset Still disease.