Interleukin-21 (IL-21) is a cytokine that has potent regulatory effects on cells of the immune system, including natural killer (NK) cells and cytotoxic T cells that can destroy virally infected or cancerous cells. This cytokine induces cell division/proliferation in its target cells. IL-21 is expressed in activated human CD4 T cells but not in most other tissues. In addition, IL-21 expression is up-regulated in Th2 and Th17 subsets of T helper cells, as well as T follicular cells. Furthermore IL-21 is expressed in NK T cells regulating the function of these cells. IL-21 has pathologic function in immune-inflammatory diseases. Data suggest the existence of a positive autocrine loop that could help to amplify and stabilize IL-21-driven, T cell-mediated responses. Moreover, it has antitumour activity and may have a role in the development of autoimmunity. IL-21 may have therapeutic potentials as an antitumor agent in the clinic.