Interleukin 18 (IL-18), a member of the IL-1 superfamily of cytokines has been demonstrated to be an important mediator of both innate and adaptive immune responses. Several reports have implicated its role in the pathogenesis of rheumatoid arthritis (RA). Although biologic therapy is firmly established in the treatment of a number of inflammatory diseases including RA, partial and non-responder patients constitute residual unmet clinical need. The aim of this article is to briefly review the biology of, and experimental approaches to IL-18 neutralisation, together with speculation as to the relative merits of IL-18 as an alternative to existing targets.