Nrf2/ARE signaling pathway can be considered a promising target for novel therapies of several disorders inclusive epilepsy, particularly when new compounds, possessing inhibitory activity against protein–protein interaction (PPI) between Nrf2 and its repressor protein Keap 1, with less of “off-target” effects and, importantly, with an optimal permeability and bioavailability properties, become available commercially. This evidence concerns the gene NFE2L2 and epilepsy.