The role of Notch in the immune system was first described in the late 90s. Reports revealed that Notch is one of the most conserved developmental pathways involved in diverse biological processes such as the development, differentiation, survival and functions of many immune populations. Here, we provide an extended view of the pleiotropic effects of the Notch signaling on the innate lymphoid cell (ILC) biology. We review the current knowledge on Notch signaling in the regulation of ILC differentiation, plasticity and functions in diverse tissue types and at both the fetal and adult developmental stages. ILCs are early responder cells that secrete a large panel of cytokines after stimulation. By controlling the abundance of ILCs and the specificity of their release, the Notch pathway is also implicated in the regulation of their functions. The Notch pathway is therefore an important player in both ILC cell fate decision and ILC immune response.
