Interleukin-21 (IL-21) is a member of the common-γ chain family of cytokines that are involved in immunoregulation. IL-21 is normally expressed by activated CD4+ T cells and is aberrantly expressed in Hodgkin lymphoma cells. The IL-21 receptor (IL-21R) activates the JAK/STAT signaling pathway and is expressed on T, B, and Natural Killer (NK) cells. Within the B cell lineage, IL-21 is a switch factor regulating IgG1 and IgG3 antibody production. IL-21 also cooperates with IL-4 for the production of multiple antibody classes in B cells. IL-21 has pleiotropic effects on the proliferation, differentiation, and effector functions of B, T, NK, and dendritic cells.