Initially described in 1989 as interferon-γ (IFN-γ) inducing factor (IGIF), interleukin-18 (IL-18) is a novel proinflammatory cytokine that is clearly more than an inducer of IFN-γ The cytokine possesses several biological properties such as activation of nuclear factor-κB (NF-κB), Fas ligand expression, the induction of both CC and CXC chemokines, and increased production of competent human immunodeficiency virus. Most activities are due to a receptor complex that recruits the IL-1 receptor-activating kinase (IRAK), leading to translocation of NF-κB. This property and others support the concept that IL-18 is related to the IL-1 family. Indeed, one of the IL-18 receptor chains is the IL-1 receptor-related protein, a member of the IL-1R family. In addition, IL-18 is structurally similar to IL-1β and like IL-1β is first synthesized as a leaderless precursor requiring the IL-1β converting enzyme for cleavage into an active molecule. The biology of IL-18 is reviewed in the overview and the implication for a role for this cytokine in disease is presented.