In this study, we review and discuss recent advancements in the regulation of the Keap1/Nrf2/ARE system and its role under physiological and pathophysiological conditions such as in exercise, diabetes, cardiovascular diseases, cancer, neurodegenerative disorders, stroke, liver and kidney system, etc. The redox-sensitive signaling system Keap1/Nrf2/ARE plays a key role in maintenance of cellular homeostasis under stress and in inflammatory, carcinogenic, and pro-apoptotic conditions, thus allowing us to consider this system as a pharmacological target. Here, NFE2L2 is linked to Stroke.