Antioxidants are used on a very large scale to try to obtain and preserve optimal health. Nutraceuticals and food supplements frequently contain huge dosages of antioxidants. It is not generally recognised that high intake of antioxidants may also have adverse effects. Three antioxidants i.e. vitamin E, beta-carotene and lipoic acid are used to illustrate general considerations on the toxicity of antioxidants. Based on the examples the following recommendations for the evaluation of the toxicity of antioxidants are made: (i) classical safety factors should not be used. (ii) Knowledge on the mechanism of the efficacy and toxicity of antioxidants should be increased. (iii) Bio-kinetic/bio-efficacy modelling might be of help to optimise dosage. (iv) When antioxidant supplementation changes into therapy, a more accurate risk/benefit analyses is warranted.