IL-27 is a heterodimeric cytokine composed of two subunits: IL-27a and IL-27b. IL-27 acts on various cell types, including T cells, B cells, macrophages, dendritic cells, natural killer (NK) cells and non-hematopoietic cells. IL-27 plays a critical role in the early regulation of T helper type 1 initiation, and enhances proliferation of naive CD4+T cells and naive B cells. It, however, also exerts anti-inflammatory functions by inhibiting the development of Th17 cells and inducing IL-10 producing type 1 regulatory T cells. IL-27 is a potentially promising cytokine for therapeutic approaches on various human diseases.