Biomarkers fulfil a crucial role in studying disease etiology, both with respect to biological plausibility, laboratory methodology, and in human studies. Markers should preferably reflect the mainstream causal process relevant to a major proportion of disease. Such markers may provide the evidence required to justify health claims regarding the role of antioxidants in the etiology of chronic diseases, e.g., cancer, cardiovascular disease and cataract. Regarding study design, type A claims, addressing enhanced biological function, would at least require human intervention studies. Type B claims, addressing reduced disease risk, would require prospective data, if possible experimental. (Nested) case control studies may be used to establish the predictive validity of precursor lesions of disease that can serve to substitute studies assessing disease occurrence as endpoints. Scientifically sound and practically feasible requirements for justification of health claims need be developed further.