Interleukin-21 is the most recently discovered member of the type-I cytokine family. Structurally, IL-21 shows homology to IL-2, IL-4, and IL-15 proteins. IL-21 shares the common gamma-chain with these three cytokines, but, in addition, binds to a unique IL-21R alpha chain, and activates the JAK/STAT pathway. IL-21 has pleiotropic actions, from augmenting the proliferation of T cells and driving the differentiation of B cells into memory cells and terminally differentiated plasma cells to augmenting the activity of natural killer cells. IL-21 is mainly produced by activated T-cells, but targets a broad range of lymphoid and myeloid cells of the immune system and therefore is able to regulate innate and acquired immune responses. 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.