The interleukin (IL)-12 family cytokine, IL-27 has been implicated in the pathogenesis of many autoimmune inflammatory disorders, including rheumatoid arthritis, psoriasis, multiple sclerosis, Crohn's disease, and ulcerative colitis. Discovered in 2002, IL-27 has been primarily described as an anti-inflammatory cytokine with regulatory roles in multiple sclerosis and experimental autoimmune encephalitis. However, recent studies have demonstrated a pro-inflammatory function of IL-27 in both the adaptive and innate immune responses. This review will focus on the proinflammatory nature of IL-27 in chronic inflammatory skin disease and inflammatory bowel disease.