In this chapter, we highlight the significance of some metabolic and biochemical issues in molecular epidemiology. We discuss biomarkers and biologically reactive intermediates and describe the significance of polymorphisms in xenobiotic metabolizing enzymes, with emphasis on the role of some of these enzymes in the generation of reactive metabolites and on the related issue of susceptibility biomarkers. In the final section, we have selected an example of a specific compound, benzene, for which a variety of different biomarkers have been studied.