This comprehensive review by Trachootham et al. explores the role of redox regulation in cell survival, focusing on the mechanisms and key players involved. The authors begin by discussing the importance of redox homeostasis, highlighting the production and elimination of reactive oxygen species (ROS) and reactive nitrogen species (RNS). They explain how oxidative stress can lead to cellular damage and contribute to various diseases, including cancer and degenerative disorders. The review then delves into the regulatory mechanisms of redox, including transcriptional regulation, direct oxidative modification, regulation of redox-sensitive proteins, and protein turnover. Key transcription factors such as NF-κB, AP-1, Nrf2, and HIF are discussed in detail, along with their roles in cell survival and how redox systems modulate their functions. The authors also examine the redox regulation of signaling proteins affecting cell death and survival, covering both the transcriptional and signal-transduction levels. They discuss the roles of mitogen-activated protein kinases (MAPKs), the PI3K/Akt pathway, caspases, Bcl-2, cytochrome c, and the integration of redox-sensitive signaling pathways. Finally, the review explores the therapeutic strategies based on redox regulation, including manipulating redox homeostasis and modulating redox-sensitive signaling molecules. The authors conclude by emphasizing the significance of understanding redox regulation in cell survival for developing treatments and preventing diseases such as cancer and degenerative disorders.This comprehensive review by Trachootham et al. explores the role of redox regulation in cell survival, focusing on the mechanisms and key players involved. The authors begin by discussing the importance of redox homeostasis, highlighting the production and elimination of reactive oxygen species (ROS) and reactive nitrogen species (RNS). They explain how oxidative stress can lead to cellular damage and contribute to various diseases, including cancer and degenerative disorders. The review then delves into the regulatory mechanisms of redox, including transcriptional regulation, direct oxidative modification, regulation of redox-sensitive proteins, and protein turnover. Key transcription factors such as NF-κB, AP-1, Nrf2, and HIF are discussed in detail, along with their roles in cell survival and how redox systems modulate their functions. The authors also examine the redox regulation of signaling proteins affecting cell death and survival, covering both the transcriptional and signal-transduction levels. They discuss the roles of mitogen-activated protein kinases (MAPKs), the PI3K/Akt pathway, caspases, Bcl-2, cytochrome c, and the integration of redox-sensitive signaling pathways. Finally, the review explores the therapeutic strategies based on redox regulation, including manipulating redox homeostasis and modulating redox-sensitive signaling molecules. The authors conclude by emphasizing the significance of understanding redox regulation in cell survival for developing treatments and preventing diseases such as cancer and degenerative disorders.