Interleukin (IL)-18 is a new member of the IL-1 family of proinflammatory cytokines. Based on preclinical studies in animals, IL-18 likely plays a role in rheumatoid arthritis, and strategies to block IL-18 activity are underway in clinical trials. In one of these trials,a naturally occurring IL-18 binding protein (IL-18 BP) binds IL-18 with a high affinity and reduces disease severity in models of inflammatory diseases. IL-18 BP is not the soluble receptor for IL-18 but rather a distinct molecule, which appears to be distantly related to the IL-1 receptor type II, both structurally and functionally, and hence represents part of the IL-1 family of receptors.