Molecular epidemiology has emerged as a natural outgrowth of attempts to apply information derived from the explosion in molecular biology to disease in human populations. The incorporation of biomarkers into classical epidemiologic designs holds the promise of unraveling mechanisms, elucidating gene-environment interactions, and dissecting heterogeneity. The primary interest of molecular epidemiology is in the identification of factors in the physical and social environment which affect the risk for disease and which are amenable to preventive intervention. The explosion in molecular technology has not, however, resulted in radical, widespread improvements in epidemiologic results and therefore has led to a sense of frustration in the public health community. As experience accumulates, there is new appreciation that attention to study design, infrastructure, and biomarker validation can improve the results.