Decrements in motor and cognitive function occur in aging, possibly due to oxidative stress-induced damage to the brain. Declines in antioxidant defense mechanisms have been postulated as a causative factor in these age-related decrements, however a clear link between oxidative stress (OS) and behavioral changes in aging has yet to be established. This review shows that age-validated psychomotor and cognitive tests are sensitive to behavioral deficits under different models of OS, including: 1) decreasing OS protection by depleting glutathione and then increasing the OS with dopamine; 2) 100% oxygen exposure; and 3) radiation. Furthermore, interventions that reduce OS result in concurrent improvements in age-associated behavioral deficits. Therefore, age-related changes in behavior may result from an inability to cope with OS that occurs throughout the life-span.