Reactive oxygen species (ROS) and NF-κB signaling are closely interconnected, with each influencing the other in complex ways. NF-κB is a family of transcription factors essential for inflammation, immunity, and various cellular processes. ROS are produced by cellular processes and can modulate NF-κB signaling, either by inhibiting or stimulating it. Conversely, NF-κB-regulated genes can influence ROS levels, affecting cellular responses to oxidative stress. NF-κB signaling is primarily regulated by IκB proteins, which inhibit DNA binding. Two main pathways activate NF-κB: the canonical (classical) pathway, involving p50 and RelA, and the noncanonical pathway, involving p52 and RelB. The canonical pathway is activated by proinflammatory signals, while the noncanonical pathway is activated by specific TNF receptor family members. ROS are generated by various cellular processes, including mitochondrial respiration, NADPH oxidases, and metabolic enzymes. These ROS can trigger both apoptotic and necrotic cell death depending on the level of oxidative stress. NF-κB plays a critical role in cell survival by upregulating antioxidant genes, such as MnSOD, Cu/Zn-SOD, and ferritin heavy chain, which help neutralize ROS. NF-κB also regulates pro-ROS enzymes, such as NADPH oxidase, Xanthine Oxidase/Dehydrogenase, and iNOS, which contribute to ROS production. ROS can influence NF-κB activation through various mechanisms, including the modification of IκB proteins, the activation of IKK complexes, and the regulation of NF-κB heterodimers. ROS can both activate and inhibit NF-κB signaling, depending on the context and the specific pathways involved. The interaction between ROS and NF-κB is complex and context-dependent, with ROS affecting NF-κB activity at multiple levels, including upstream signaling, DNA binding, and transcriptional regulation. This crosstalk is crucial for maintaining cellular homeostasis and responding to oxidative stress. Understanding these interactions is essential for developing therapeutic strategies targeting oxidative stress and inflammatory diseases.Reactive oxygen species (ROS) and NF-κB signaling are closely interconnected, with each influencing the other in complex ways. NF-κB is a family of transcription factors essential for inflammation, immunity, and various cellular processes. ROS are produced by cellular processes and can modulate NF-κB signaling, either by inhibiting or stimulating it. Conversely, NF-κB-regulated genes can influence ROS levels, affecting cellular responses to oxidative stress. NF-κB signaling is primarily regulated by IκB proteins, which inhibit DNA binding. Two main pathways activate NF-κB: the canonical (classical) pathway, involving p50 and RelA, and the noncanonical pathway, involving p52 and RelB. The canonical pathway is activated by proinflammatory signals, while the noncanonical pathway is activated by specific TNF receptor family members. ROS are generated by various cellular processes, including mitochondrial respiration, NADPH oxidases, and metabolic enzymes. These ROS can trigger both apoptotic and necrotic cell death depending on the level of oxidative stress. NF-κB plays a critical role in cell survival by upregulating antioxidant genes, such as MnSOD, Cu/Zn-SOD, and ferritin heavy chain, which help neutralize ROS. NF-κB also regulates pro-ROS enzymes, such as NADPH oxidase, Xanthine Oxidase/Dehydrogenase, and iNOS, which contribute to ROS production. ROS can influence NF-κB activation through various mechanisms, including the modification of IκB proteins, the activation of IKK complexes, and the regulation of NF-κB heterodimers. ROS can both activate and inhibit NF-κB signaling, depending on the context and the specific pathways involved. The interaction between ROS and NF-κB is complex and context-dependent, with ROS affecting NF-κB activity at multiple levels, including upstream signaling, DNA binding, and transcriptional regulation. This crosstalk is crucial for maintaining cellular homeostasis and responding to oxidative stress. Understanding these interactions is essential for developing therapeutic strategies targeting oxidative stress and inflammatory diseases.