Oxidative stress is an imbalance between oxidants and antioxidants in favor of the oxidants, resulting in disruption of redox signaling and control and causing molecular damage. Oxidative stress is related to a variety of diseases, for example, cardiovascular diseases, neurodegenerative diseases, infections, and cancer. It might be that oxidative stress, and, more specifically, reactive oxygen species (ROS), affects longevity in a subtle way through signaling. Possible therapies to reduce oxidative stress in the elderly are nutritional intervention (for example, caloric restriction (CR)) and exercise. Exercise is associated with favorable changes in the expression of antioxidant enzymes and the oxidative stress status in general. A diet with CR also seems to be a promising way to reduce oxidative stress by decreasing oxidant emission and improving antioxidant mechanisms. A better understanding of where the antioxidant mechanisms in the elderly fail could be a big step forward in developing new therapies (such as exercise or diet) that prevent oxidative damage and cellular dysfunction with age.