Cytokine-mediated immunity plays a crucial role in the pathogenesis of various diseases including autoimmunity. Recently, interleukin-27 (IL-27) was identified, which, along with IL-12, IL-23, and IL-35, belongs to the IL-12 cytokine family. These family members play roles in the regulation of T helper (Th) cell differentiation. IL-27 is unique in that while it induces Th1 differentiation, the same cytokine suppresses immune responses. In the absence of IL-27-mediated immunosuppression, hyper-production of various pro-inflammatory cytokines concomitant with severe inflammation in affected organs was observed in IL-27 receptor alpha chain (WSX-1)-deficient mice infected with Trypanosoma cruzi. Experimental allergic or inflammatory responses were also enhanced in WSX-1-deficient mice. The immunosuppressive effects of IL-27 depend on inhibition of the development of Th17 cells (a newly identified inflammatory T-helper population) and induction of IL-10 production. Moreover, administration of IL-27 or augmentation of IL-27 signaling suppresses some diseases of autoimmune or allergic origin, demonstrating its potential in therapy of diseases mediated by inflammatory cytokines. In this review, we discuss recent studies on the role of IL-27 in immunity to parasitic and bacterial infections as well as in allergy and autoimmunity in view of its pro- and anti-inflammatory properties.