Often, attention is drawn to the potential for neurodevelopmental damage after a man-made disaster or accidental poisoning event, as occurred with PCBs, methyl-mercury, and most recently, with lead in Flint, Michigan. Those earlier tragedies, which led to serious mental and physical disabilities, served as warning signs and led to in-depth research on lower level exposures to the same substances, levels for which clinical signs are not obvious, yet large epidemiologic studies have now uncovered the adverse consequences. In this panel, Dr. Lanphear describes how low-level exposures have been dismissed, even when comparisons with known toxins or drugs that trigger problems at similarly low doses indicate reasons for concern. His presentation outlines what clinicians and scientists need to know about the biologic impacts from lead, arsenic, and other exposures in early development. Dr. Rauh uses novel approaches in a longitudinal study to examine how commonplace prenatal exposures may have long term impacts, and how imaging studies are showing changes that correlate with gestational pesticide exposures. Her team has also identified surprising neurologic outcomes in school-aged children. Dr. Engel takes a step back to consider various biomarkers and how to circumvent the common pitfalls in environmental epidemiology and strengthen the inferences that can be made with regard to causal relationships, based not only on consistency and replication across studies but also on temporality, mechanistic considerations, dose-response, and other attributes of observational studies. Dr. Fallin will lay out a framework for integrating research on genetics with environmental epidemiology to harness the power of -omics technology with large-scale well-designed epidemiologic studies to advance the science of etiology in its multi-factorial complexity.