Nrf2 is a transcription factor that regulates the expression of genes involved in antioxidant and detoxification processes, playing a crucial role in cellular defense against oxidative and xenobiotic stress. This review discusses the various modes of Nrf2 regulation, including its interaction with Keap1, the Nrf2-Keap1-ARE pathway, and its involvement in other cellular processes such as autophagy, intermediary metabolism, and stem cell quiescence. Nrf2 is tightly regulated at multiple levels, including transcriptional, post-transcriptional, and post-translational, and its activity is essential for maintaining redox homeostasis. Nrf2 regulates the expression of genes involved in glutathione synthesis, thioredoxin-based antioxidant systems, NADPH regeneration, heme metabolism, and xenobiotic detoxification. It also plays a role in the unfolded protein response, proteasome activity, and the regulation of intermediary metabolism. The regulation of Nrf2 activity involves interactions with various proteins, including sMaf proteins, and is influenced by transcription factors, post-transcriptional modifications, and the availability of binding partners. Nrf2 is involved in the regulation of gene expression through the recruitment of co-activators and chromatin remodelers, and its activity is influenced by kinases such as PKC and ERK. The Nrf2-regulated network is complex and involves multiple interactions, and understanding its regulation is essential for developing therapeutic strategies for diseases related to oxidative stress and xenobiotic exposure. The study of Nrf2's regulatory mechanisms provides insights into its role in cellular defense and its potential as a therapeutic target.Nrf2 is a transcription factor that regulates the expression of genes involved in antioxidant and detoxification processes, playing a crucial role in cellular defense against oxidative and xenobiotic stress. This review discusses the various modes of Nrf2 regulation, including its interaction with Keap1, the Nrf2-Keap1-ARE pathway, and its involvement in other cellular processes such as autophagy, intermediary metabolism, and stem cell quiescence. Nrf2 is tightly regulated at multiple levels, including transcriptional, post-transcriptional, and post-translational, and its activity is essential for maintaining redox homeostasis. Nrf2 regulates the expression of genes involved in glutathione synthesis, thioredoxin-based antioxidant systems, NADPH regeneration, heme metabolism, and xenobiotic detoxification. It also plays a role in the unfolded protein response, proteasome activity, and the regulation of intermediary metabolism. The regulation of Nrf2 activity involves interactions with various proteins, including sMaf proteins, and is influenced by transcription factors, post-transcriptional modifications, and the availability of binding partners. Nrf2 is involved in the regulation of gene expression through the recruitment of co-activators and chromatin remodelers, and its activity is influenced by kinases such as PKC and ERK. The Nrf2-regulated network is complex and involves multiple interactions, and understanding its regulation is essential for developing therapeutic strategies for diseases related to oxidative stress and xenobiotic exposure. The study of Nrf2's regulatory mechanisms provides insights into its role in cellular defense and its potential as a therapeutic target.