Aging is associated with a general decline in physiological functions including cognitive functions. Given that the hippocampus is known to be critical for certain forms of learning and memory, it is not surprising that a number of neuronal processes in this brain area appear to be particularly vulnerable to the aging process. Long-term potentiation (LTP), a form of synaptic plasticity that has been proposed as a biological substrate for learning and memory, has been used to examine age-related changes in hippocampal synaptic plasticity. A current hypothesis states that oxidative stress contributes to age-related impairment in learning and memory. This is supported by a correlation between age, memory impairment, and the accumulation of oxidative damage to cellular macromolecules. However, it also has been demonstrated that ROS are necessary components of signal transduction cascades during normal physiological processes. This review discusses the evidence supporting the dual role of reactive oxygen species (ROS) as cellular messenger molecules in normal LTP, as well their role as damaging toxic molecules in the age-related impairment of LTP. In addition, we will discuss parallel analyses of LTP and behavioral tests in mice that overexpress antioxidant enzymes and how the role of antioxidant enzymes and ROS in modulating these processes may vary over the lifespan of an animal.