Life is inseparable from oxygen. The redox state in cells directly regulates the functions of biomacromolecules and mediates cell signal transduction and many physiological and pathological processes such as aging, neurodegenerative diseases, cardiovascular diseases, metabolic diseases, and tumors. In view of The Free Radical Theory of Aging proposed in the 1950s, oxidative stress has long been confused with oxidative damage and is regarded as bad. Antioxidation once became synonymous of “anti-aging”. Here in combination the relevant research work of our laboratory and the frontiers of the redox biology field, we propose three new understandings of “oxidative stress”. (1) Oxidative stress is not equal to oxidative damage and has important physiological functions. (2) Oxidative stress is not related to all physiological and pathological processes without specificity, while redox regulation is specific and redox modification of biomacromolecules is the mechanism. (3) Non-targeting antioxidants do not work well, the redox balance has precise properties, 5R principle should be considered for antioxidant pharmacology and the new era of precision redox medicine has begun. Future challenges are reflected in three major aspects: basic research on redox biology and medicine, the specific molecular mechanisms of oxidative stress in physiological and pathological processes and environmental stress, and precise redox intervention against aging and diseases. Multidisciplinary basic research, in-depth cooperation between basic research and clinical research and international collaboration must be enhanced to achieve breakthroughs in the understanding of redox in life processes, breakthroughs in redox mechanisms, and breakthroughs in precision intervention!