The article explores the interdependence between oxidative stress and inflammation, which are closely related pathophysiological processes that play significant roles in the development of chronic diseases. Oxidative stress, characterized by an imbalance between prooxidants and antioxidants, can lead to tissue damage and molecular alterations, while inflammation involves the infiltration of immune cells and the release of reactive species that further exacerbate oxidative stress. The article discusses the complex relationship between these two processes, highlighting how one can trigger the other and contribute to the pathogenesis of diseases such as diabetes, cardiovascular disease, neurodegenerative diseases, and cancer. The failure of antioxidant trials in preventing or treating these diseases is attributed to the inability to selectively target both oxidative stress and inflammation or the use of nonselective agents that may block some pathways but exaggerate others. The review also examines the role of transcription factors like nuclear factor-κB (NF-κB) in the activation of both oxidative stress and inflammation, and suggests that a comprehensive approach targeting both processes is necessary for effective treatment. Finally, the article proposes that the antioxidant paradox may be explained by the interdependence between oxidative stress and inflammation, emphasizing the need for careful selection and quantification of redox and inflammatory status in clinical trials.The article explores the interdependence between oxidative stress and inflammation, which are closely related pathophysiological processes that play significant roles in the development of chronic diseases. Oxidative stress, characterized by an imbalance between prooxidants and antioxidants, can lead to tissue damage and molecular alterations, while inflammation involves the infiltration of immune cells and the release of reactive species that further exacerbate oxidative stress. The article discusses the complex relationship between these two processes, highlighting how one can trigger the other and contribute to the pathogenesis of diseases such as diabetes, cardiovascular disease, neurodegenerative diseases, and cancer. The failure of antioxidant trials in preventing or treating these diseases is attributed to the inability to selectively target both oxidative stress and inflammation or the use of nonselective agents that may block some pathways but exaggerate others. The review also examines the role of transcription factors like nuclear factor-κB (NF-κB) in the activation of both oxidative stress and inflammation, and suggests that a comprehensive approach targeting both processes is necessary for effective treatment. Finally, the article proposes that the antioxidant paradox may be explained by the interdependence between oxidative stress and inflammation, emphasizing the need for careful selection and quantification of redox and inflammatory status in clinical trials.