In the etiologic investigation of complex diseases and neuro-developmental disorders, the interaction of genetic factors and the environment have been evaluated by comparing disease risk as a function of environmental exposure in individuals who carry genetic variants of interest. While advances in technology have improved classification of genetic variant data, methods to ascertain environmental exposures remain largely underdeveloped. In this editorial, we discuss how mitotically heritable epigenetic marks in imprint regulatory elements may potentially serve as genome-wide biosensors of exposure, thereby reducing exposure misclassification, especially in studies evaluating the early origins of adult disease. Development of epigenetic biosensors for exposure monitoring will require a concerted effort in not only demonstrating that they are a stable record of past exposures, but also that the epigenetic marks are causally related to exposure.