AbstractStrong evidence implicatesmaternal environmental exposures in contributing to adverse outcomes during preg-nancy and later in life through the developmental origins of health and disease hypothesis. Recent research suggests these effects are mediated through the improper regulation of DNA methylation in offspring tissues, specifically placental tissue, which plays a critical role in fetal development. This article reviews the relevant literature relating DNA methylation in multiple tissues at or near delivery to several prenatal environ-mental toxicants and stressors, including cigarette smoke, en-docrine disruptors, heavy metals, as well as maternal diet. These human studies expand upon previously reported out-comes in animal model interventions and include effects on both imprinted and non-imprinted genes. We have also noted some of the strengths and limitations in the approaches used, and consider the appropriate interpretation of these findings in terms of their effect size and their relationship to differential gene expression and potential health outcomes. The studies suggest an important role of DNA methylation in mediating the effects of the intrauterine environment on children’shealth and a need for additional research to better clarify the role of this epigenetic mechanism as well as others.