Cytokines are of major importance in periodontal disease progression. It is generally agreed that control of the Th1/Th2 balance is central to the immunoregulation of periodontal disease. There is increasing evidence in humans that the stable periodontal lesion is mediated by Th1 cells, while the progressive lesion sees a shift toward Th2 cells. Equally, there is conflicting evidence, mainly in animal models, that bone loss is mediated by Th1 responses, and that Th2 responses are protective. In the presence of IL-12, IL-18 induces Th1 responses while, in the absence of IL-12, it promotes Th2 responses. It is clear, therefore, that since IL-18 has the ability to induce either Th1 or Th2 differentiation, it becomes important to consider its role in periodontal disease. This review endeavors to give an overview of this cytokine and its relevance for periodontal disease.