IL-7 was initially described as a stromal derived factor which is capable of inducing the growth of pre-B cells in vitro. IL-7 acts on a variety of cells through its receptor (IL-7R), a heterodimer consisting of IL-7Rα (CD127) and a common γc chain (CD132) shared by other cytokine (IL-2, IL-4, IL-9, IL-15, and IL-21) receptors. In addition, IL-7Rα is shared with TSLP. The generation of IL-7-deficient and IL-7Rα-deficient mice and monoclonal antibody blocking experiments confirmed the requirement of IL-7 for B-cell development in mice. Nevertheless, mutations in the α chain of the IL-7 receptor in patients with severe combined immunodeficiency (SCID) confirmed that IL-7 is indispensable for T-cell development in humans. However, the presence of B cells in these individuals suggests important differences between the role of IL-7 in murine and human lymphocyte development. Thus, although human B-cell development does not appear to require IL-7, immature human B cells do proliferate in response to IL-7.? Nevertheless, most recent information suggests that IL-7 dependence in human lymphopoiesis increases during the progression of ontogeny in cord blood and bone marrow. IL-7 can be associated to hepatocyte grow factor (HGFβ) to form a hybrid cytokine (IL-7/HGFβ), which induces greater proliferation of CFU-S, SLPs, and pre–pro-B cells than does native IL-7. The hybrid cytokine signals through both IL-7R (IL-7Rα plus γc) and c-Met. Soluble forms of the IL-7R α chain (sCD127) have been identified. They are derived from alternative splicing and by release of membrane-bound sCD127. sCD127 acts as an antagonist and is increased by immune activation. sCD127 concentration is increased in Type I diabetes patients, and it is glycated. The glycated form does not act as an antagonist of IL-7–mediated T-cell expansion. Alterations of the soluble form of IL-7Ra influences risk of multiple sclerosis.