This publication seeks to provide a framework for selecting and validating biomarkers for risk assessment. Initial chapters consider the role of biomarkers in risk assessment and their validity. A biomarker is any substance, structure or process that can be measured in the body or its products, and influence or predict the incidence of outcome or disease. Biomarkers can be classified into markers of exposure, effect and susceptibility. If biomarkers are to contribute to environmental and occupational health risk assessments, they have to be relevant and valid. Relevance refers to the appropriateness of biomarkers to provide information on questions of interest and importance to public and environmental health authorities and other decision-makers. The validity of a biomarker is a function of intrinsic qualities of the biomarker and characteristics of the analytic procedures. Additionally, three broad categories of validity can be distinguished: measurement validity, internal study validity and external validity. Measurement validity is the degree to which a biomarker indicates what it purports to indicate. Internal study validity is the degree to which inferences drawn from a study actually pertain to study subjects and are true. External validity is the extent to which findings of a study can be generalized to apply to other populations. Subsequent chapters examine the validation of specific types of biomarkers and cross-species comparability. Supporting the main text are four extensive appendices covering the following subjects: 1. Biomarkers of exposure and effect for carcinogenicity 2. Biomarkers of exposure and effect for non-carcinogenic end-points 3. Measurement of drug metabolizing enzyme polymorphisms as indicators of susceptibility 4. Validation of biomarkers for environmental health research and risk assessment