The debilitating consequences of age-related brain deterioration are widespread and extremely costly in terms of quality of life and longevity. One of the potential major causes of age-related destruction of neuronal tissue is toxic free radicals that are a natural result of aerobic metabolism. The brain is particularly susceptible to free radical attack because it generates more of these toxicants per gram of tissue than does any other organ. The major defense mechanisms the brain uses to combat reducing equivalents is via their enzymatic metabolism. The vitamin antioxidants, vitamin E (alpha-tocopherol in particular) and vitamin C (ascorbate), also aid in protecting the brain from oxidative stress by directly scavenging toxic radicals. A newly discovered, potentially highly important antioxidant in the brain is the indole melatonin. The pineal hormone melatonin is rapidly taken up by the brain. In vitro melatonin is more effective than glutathione in scavenging the highly toxic hydroxyl radical and also more efficient than vitamin E in neutralizing the peroxyl radical. Furthermore, it stimulates the main antioxidant enzyme of the brain, glutathione peroxidase. In vivo melatonin is a potent antioxidant and it lacks prooxidant actions.