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IL-27 is a pleiotropic cytokine with distinct immunomodulatory activities under physiological and pathological conditions. IL-27 enhances the function of Th1 and CD8+ T cells, promotes the development of Tfh and Tr1, and inhibits the function of Th2, Treg, Th9 and Th17 cells. IL-27 is also involved in regulating the immune response of B cells, NK cells, DCs and macrophages. IL-27 production is tightly regulated at both transcriptional and post-transcriptional levels. Given its wide-ranging effects on immune regulation, IL-27 has been implicated in the pathogenesis of autoimmune and infectious diseases, as well as cancer.