The rapid rate of discovery and development in the nanotechnology field will undoubtedly increase both human and environmental exposures to engineered nanomaterials. Whether these exposures pose a significant risk remains uncertain. Despite recent collective progress there remain gaps in our understanding of the nanomaterials physiochemical properties that drive or dictate biological responses. The development and implementation of rapid relevant and efficient testing strategies to assess these emerging materials prior to large-scale exposures could help advance this exciting field. I present a powerful approach that utilizes a dynamic in vivo zebrafish embryonic assay to rapidly define the biological responses to nanomaterial exposures. Early developmental life stages are often uniquely sensitive to environmental insults, due in part to the enormous changes in cellular differentiation, proliferation and migration required to form the required cell types, tissues and organs. Molecular signaling underlies all of these processes. Most toxic responses result from disruption of proper molecular signaling, thus, early developmental life stages are perhaps the ideal life stage to determine if nanomaterials perturb normal biological pathways. Through automation and rapid throughput approaches, a systematic and iterative strategy has been deployed to help elucidate the nanomaterials properties that drive biological responses.