This review will discuss the evidence for activation of nuclear factor erythroid 2-related factor 2 (Nrf2) in neurodegeneration, pharmacological and genetic targeting of Nrf2, and in which cells Nrf2 is activated, focusing on Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, Huntington’s disease and multiple sclerosis. This evidence concerns the gene NFE2L2 and multiple sclerosis.