This chapter first discusses the urgent need for prevention of childhood diseases that impose a huge and growing burden on families and society. It provides a review of recent research in this area to illustrate both the strengths and limitations of molecular epidemiology in drawing needed links between environmental exposures and illness in children. For illustration, three of the major diseases in children are discussed: asthma, cancer and developmental disorders. All three impose significant difficulties, have increased in recent decades, and are thought to be caused in substantial part by environmental factors, such as toxic exposures due to lifestyle choices (i.e. smoking and diet), pollutants in the workplace, ambient air, water and the food supply. These exogenous exposures can interact with "host" factors, such as genetic susceptibility and nutritional deficits, to cause disease. Molecular epidemiology has provided valuable new insights into the magnitude and diversity of exposures beginning in utero, the unique susceptibility of the young, and the adverse preclinical and clinical effects resulting from the interactions between these factors. However, molecular epidemiology also faces certain constraints and challenges that are specific to studies of the very young, including ethical issues, technical issues due to the limited amount of biological specimens that can be obtained, and communication of results to parents and communities. These challenges are particularly apparent when incorporating the newer epigenetic and "omic" techniques and biomarkers into studies of children's diseases.