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Reactive oxygen species (ROS) have traditionally been viewed as pathological by-products of metabolism that drive tissue damage through oxidative stress. However, accumulating evidence across chronic diseases, including metabolic, cardiovascular, neurodegenerative disorders, and cancer, indicates that ROS also function as tightly regulated signaling molecules essential for cellular adaptation and survival. This paradigm shift from oxidative stress to redox signaling necessitates a fundamental re-evaluation of how redox imbalance contributes to chronic disease pathogenesis. In this review, we propose that chronic diseases should be understood as disorders of maladaptive redox homeostasis rather than simple consequences of excessive oxidative damage. We delineate the distinction between oxidative stress and redox signaling, emphasizing how chronic redox remodeling stabilizes pathological cellular states through coordinated regulation of key redox-sensitive transcriptional nodes, including KEAP1-NRF2, FOXO, HIFs, and NF-κB. Using cancer as a representative model, we illustrate how elevated but buffered ROS levels support oncogenic signaling, metabolic rewiring, and therapeutic resistance through redox addiction. We further discuss why non-specific antioxidant strategies have largely failed and argue that effective intervention requires context-dependent redox modulation rather than global ROS suppression. Finally, we introduce therapeutic redox reprogramming and outline future directions for precision redox medicine based on biomarker-guided stratification and disease stage-specific targeting strategies.