Interleukin (IL)-18 is a member of the IL-1 cytokine family. Pro-IL-18 is cleaved by caspase-1 (IL-1beta-converting enzyme) to yield biologically active 18-kDa IL-18. Interleukin-18 is recognized by a heterodimeric receptor, consisting of a ligand-binding alpha-chain (IL-18Ralpha/IL-1Rrp) and an associating beta-chain (IL-18Rbeta/AcPL), which transmits signals through MyD88/IRAK/TRAF-6 molecules. Interleukin-18 is expressed in various types of cells, including macrophages, keratinocytes, intestinal epitherial cells, osteoblastic cells, chondrocytes, and adrenal cortex cells. Interleukin-18 promotes IFN-gamma production and Th1 helper T-cell development, synergistically with IL-12. However, IL-18 itself shows capabilities to induce IL-4, IL-5, IL-10, and IL-13 from T and natural killer cells. It also induces PGE2 production from activated macrophages. Moreover, many diseases are characterized by the production of IL-18 in the lesion. Taking these data together, our working hypothesis on how IL-18 is involved in "destructive" and "compensatory" pathways is proposed in this issue.