Interleukin-18 (IL-18), a recently identified immunoregulatory and inflammatory cytokine, has attracted a profound interest as a potential therapeutic target in autoimmune/inflammatory disorders. In this review the authors focus on: IL-18 biology as an important link between innate and adaptive immunity; evidence of its pro-inflammatory role in several human autoimmune and chronic inflammatory disorders; and data indicating that IL-18 blockade in animal models results in prevention/amelioration of the disease process and preservation of the target tissue integrity and function. Finally, the authors analyse strategies presently under development to block IL-18 function and potential pitfalls resulting from IL-18 blockade that should be considered in ongoing/future clinical trials.