Interleukin‐21 (IL‐21) is the newest member of the common γ‐chain family of cytokines, which includes IL‐2, IL‐4, IL‐7, IL‐9, IL‐13, and IL‐15. Its private receptor, IL‐21R, has been shown to activate the Janus kinase/signal transducers and activators of transcription signaling pathway upon ligand binding. Initial studies have demonstrated that IL‐21 has pleiotropic effects on the proliferation, differentiation, and effector functions of B, T, natural killer, and dendritic cells. More recently, the potential therapeutic capacity of IL‐21 in the treatment of cancers has been widely investigated. The biological role of IL‐21 in the immune system is complex, as IL‐21 has been shown to have the ability to both promote and inhibit immune responses. Overall, the current data point to IL‐21 being a novel immunomodulatory cytokine, whose regulation of any given immune response is highly dependent on the surrounding environmental context.