IL-18 was first identified as IFN-inducing factor (IGIF). It is a member of the IL-1 family of cytokines and similar to IL-1β, IL-18 is initially synthesized as an inactive precursor without a signal peptide and is cleaved into the mature form by activated caspase 1. Caspase I-independent maturation of IL-18 is induced by FASL. Mature IL-18 binds directly to the IL-18 receptor alpha chain and then recruits IL-18 receptor beta chain to form a high affinity complex. The high affinity complex recruits MyD88 and leads to IRAK/TRAF6 pathway activation and NF-κB nuclear translocation. IL-18 in combination with IL-12 shows a synergistic effect on IFNβ production; without costimulation, IL-18 alone does not induce IFNβ production. IL-18 can induce IFNβ production from splenocytes, liver macrophage, T lymphocytes and natural killer cells. IL-18 also enhances the production of GM-CSF and IL-12. IL-18 enhances Th1 cell development by synergizing with IL-12 and promotes Th2 cell differentiation in the presence of TCR activation. IL-18 plays a major role in autoimmune and inflammatory diseases. It has been implicated in many diseases such as eczema, psoriasis, inflammatory bowel disease, metabolic syndromes, hemophagocytic syndrome, sepsis and acute kidney injury. Blocking of IL-18 activity has been an attractive therapeutic approach for autoimmune disease. It has been shown that neutralization of IL-18 has reduced both intestinal IFNβ and TNFα production and resulted in a dose dependent reduction in colitis severity in mice. IL-18 is also able to induce angiogenesis, migration, proliferation and immune escape, and has been associated with cancer. Several publications show that IL-18 gene polymorphism may be risk factors for several cancers.