In this review, we discuss recent progress from studies on the biology of IL-21 and the role of this cytokine in the pathogenesis of autoimmunity. Recent studies have demonstrated that IL-21 plays an important and non-redundant role in a number of autoimmune animal models indicating that IL-21 could be a common modulator of the adaptive immune response towards self-tissue constituents in diseases such as systemic lupus erythematosus, models of rheumatoid arthritis, multiple sclerosis and type-1 diabetes. Also, the studies on the production of IL-21 in human autoimmune diseases and its behaviour on human cells in vitro are revealing the potential of IL-21 to exacerbate cellular processes that determine the course of autoimmune diseases.