Advances in the environmental health sciences – from high-throughput cell-based in vitro studies to environment-wide association studies – have led to new approaches to understanding the toxicity of chemicals in humans. These approaches are faster, less expensive, and potentially more comparable to human exposures than legacy animal toxicity testing approaches. However, many questions remain about whether and how to make the paradigm shift to using new data streams as the basis for the wide array of research, policy, and regulatory decisions.