With the mass production of engineered nanoparticles, risk assessment efforts are in need of platforms that offer predictive value to human health and environment, and also possess high throughput screening capacity. Scientists, when turning to a model-organism to help answer genetic questions that cannot be easily addressed in humans, often chose the zebrafish. However, the current screening process in zebrafish involves mostly counting the survival rate, hatching and developmental abnormalities etc. through visual examination of each embryo and/or larvae under a dissecting microscope. Such process is time-consuming, labor-intensive and has limitations on data acquisition as well as statistics analysis. Researchers have now successfully demonstrated two high content imaging platforms to enhance the ability to screen the toxicological effects of nanoparticles in zebrafish embryos.