Interleukin (IL-) 27 is a helical cytokine of the greater IL-6/IL-12 family with a broad range of pro- and anti-inflammatory properties. It can skew T helper cell development, suppress T cell proliferation, stimulate cytotoxic T cell activity, induce isotype switching in B cells, and has diverse effects on innate immune cells. In vivo, its most important role appears to be that of immune regulation, as mice with defects in IL-27 or its receptor display enhanced immune responses in a range of infectious and noninfectious situations. In this review, we discuss the body of knowledge on IL-27 and its potential therapeutic utility.