The relationship between exposure and disease when biomarkers are introduced in an epidemiologic study is explored and summarized. In molecular epidemiologic studies, biologic measurements play a major role as markers of exposure, disease or susceptibility to disease and/or exposure. In this scenario, the definition and management of confounding factors may change. Sometimes the presence or activation of the biomarker is partially caused by the relevant environmental exposure, and therefore the 2 variables (exposure and biomarker) should not be always treated as confounders of each other. Models of exposure-disease association in the presence of biologic markers are presented. The concept of confounders is reviewed in light of the role of biomarkers in the pathway between exposure and disease. © 2002 Wiley-Liss, Inc.