Interleukin-18 (IL-18) is a proinflammatory cytokine that belongs to the IL-1 cytokine family, due to its structure, receptor family and signal transduction pathways. Similarly to IL-1beta, IL-18 is synthesized as a precursor requiring caspase-1 for cleavage into an active IL-18 molecule. However, with regard to its capacity to induce the production of Th1 cytokines and to enhance cell-mediated cytotoxicity, IL-18 is also related to IL-12. Produced mainly by antigen-presenting cells, IL-18 is a pleiotropic factor involved in the regulation of both innate and acquired immune responses, playing a key role in autoimmune, inflammatory, and infectious diseases. This review summarizes recent advances in the understanding of IL-18 structure, processing, receptor expression, and immunoregulatory functions and emphasizes the critical role of this cytokine in bacterial infections. It focuses on the participation of this cytokine in the defense against intracellular bacteria, including Listeria, Shigella, Salmonella, and Mycobacterium tuberculosis. Since this cytokine may be particularly useful in immunoprophylactic and immunotherapeutic interventions in which the cellular response is most desirable, the potential therapeutic aspects of IL-18 is also discussed.