Interleukin (IL)-27 is a novel cytokine secreted by stimulated antigen-presenting cells. Initial studies on the biology of IL-27 provided evidence for its role in the initiation of T(H)1 responses; however, subsequent work has indicated that IL-27 has broad inhibitory effects on T(H)1, T(H)2, and T(H)17 subsets of T cells as well as the expansion of inducible regulatory T cells. The involvement of IL-27 in the regulation of angiogenesis and antiviral response has also recently been reported. The aim of this review is to highlight the potential areas of IL-27 clinical application, especially the management of neoplastic and viral diseases as well as autoimmune disorders, including rheumatoid arthritis and multiple sclerosis. The review will also serve to elaborate on the molecular mechanisms involved in the expression of this cytokine and signaling from the IL-27 receptor.