We will discuss (1) how modulation of GADD45 expression in nerve and glial damage, oxidative stress, DNA damage repair, apoptosis, proliferation, differentiation, inflammation, and neuroplasticity; (2) how studies in human patient tissues, as well as in vitro and in vivo model systems, have uncovered the roles of GADD45 in central nervous system diseases. The gene discussed is GADD45A; the disease is central nervous system disorder.