Nuclear Factor-Erythroid Factor 2 (Nrf2) is an important transcription factor that regulates the expression of large number of genes in healthy and disease states. Nrf2 is made up of 605 amino acids and contains 7 conserved regions known as Nrf2-ECH homology domains. Nrf2 regulates the expression of several key components of oxidative stress, mitochondrial biogenesis, mitophagy, autophagy and mitochondrial function in all organs of the human body, in the peripheral and central nervous systems. Mounting evidence also suggests that altered expression of Nrf2 is largely involved in aging, neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's diseases, Amyotrophic lateral sclerosis, Stroke, Multiple sclerosis and others. The purpose of this article is to detail the essential role of Nrf2 in oxidative stress, antioxidative defense, detoxification, inflammatory responses, transcription factors, proteasomal and autophagic/mitophagic degradation, and metabolism in aging and neurodegenerative diseases. This article also highlights the Nrf2 structural and functional activities in healthy and disease states, and also discusses the current status of Nrf2 research and therapeutic strategies to treat aging and neurodegenerative diseases.