Several pathological conditions are believed to be causally related to the generation of reactive oxygen species and free radicals including various neurodegenerative disorders. In the histopathology of Alzheimer's disease (AD) many signs of oxidative reactions can be found building the basis of the oxidative stress hypothesis of AD. One major player in the generation of an overall oxidative microenvironment for the nerve cells is the amyloid beta protein (A beta) of the senile plaques in brain areas affected in AD. A beta can be neurotoxic and this toxicity is mediated by peroxides and by the peroxidation of membrane lipids leading to the lysis of the cell. Consequently, lipophilic free radical scavengers such as vitamin E and the recently discovered antioxidant activity of the female sex hormone estrogen protects neurons against the oxidative toxicity of A beta and other AD-related oxidative insults. In a first clinical trial using vitamin E in therapy, this antioxidant could slow down the course of the disease launching further clinical investigations. Although antioxidants act as non-specific protective chemical shields for neurons and do not target specific pathological events, they are highly effective and further investigations on their activity might lead to an even more effective application of antioxidants. Since the knowledge of the pathways of neuronal cell death that occur during oxidative challenges is increasing, it will be of central interest how antioxidants can interfere with signal transduction mechanisms and therefore also modify genetic programs. As long as specific interventions are not available the optimistic data concerning the neuroprotective activity of antioxidants in vitro and in vivo underline an important role for antioxidative acting compounds for the prevention and therapy of oxidative stress-related conditions including AD.