Therapeutic interventions for the prodromal stages of dementia are currently being sought with a view to delaying if not preventing disease onset. Uncertainty as to whether cognitive disorder in a given individual will progress towards dementia and adverse drug side effects has led to hesitancy on the part of drug regulators to instigate preventive pharmacotherapies. In this context, antioxidant therapies may provide a low-risk alternative, targeting very early biological changes. While a growing body of knowledge demonstrates both the importance of oxidative stress in the aetiology of dementia and the efficacy of antioxidant treatment in animal and cellular models, studies in humans are presently inconclusive. While some antioxidants, notably flavonoid- or vitamin-rich diets, appear to lower the relative risk for Alzheimer’s disease in humans in observational studies, these results must be interpreted in the light of the biological complexity of the relationship between oxidative stress and neurodegeneration, and the methodological and theoretical shortcomings of studies conducted to date. A clearer understanding of these factors will assist in the interpretation of the results of the intervention studies which are now being undertaken; these studies being the only current means of establishing efficacy for preventive drug treatment of Alzheimer’s disease.