Dysregulated cell-mediated immune responses may lead to chronic inflammation and autoimmune disorders. The recent discovery of the dimeric interleukin (IL)-12-related cytokine IL-23 now adds to our understanding of the fine-tuning of cellular immunity. The critical implication of the role that IL-12p40 plays in autoimmune inflammation has long been misinterpreted and only recently have studies revealed that it is IL-23, and not IL-12, that is the decisive factor in this immune deviation. Therefore, targeting of IL-23 or the IL-23 receptor is a promising therapeutic approach for autoimmune diseases. This review summarizes recent findings regarding IL-23-mediated autoreactive inflammatory responses, and introduces possible therapeutic interventions that are aimed at mitigating autoimmune inflammation.