Oxidative stress is defined by an imbalance between increased levels of reactive oxygen species (ROS) and a low activity of antioxidant mechanisms. An increased oxidative stress can induce damage to the cellular structure and potentially destroy tissues. However, ROS are needed for adequate cell function, including the production of energy by the mitochondria. Increased oxidative stress has been incriminated in physiological conditions, such as aging and exercise, and in several pathological conditions, including cancer, neurodegenerative diseases, cardiovascular diseases, diabetes, inflammatory diseases, and intoxications. However, prevention by antioxidants has been mostly inefficient. Therefore, a rigorous scientific evaluation in well-defined conditions is mandatory to define the appropriate place for manipulations of the oxidative pathways in human medicine.