Nanomaterials are increasingly employed in a wide variety of applications, ranging from electronics to nanomedicine. However, not much is known on the impact that nanomaterials could have on human health and environment. Thereby, to fill this gap of knowledge, in the last decade, toxicity studies were strongly promoted by the scientific community. In this framework, zebrafish (Danio rerio) represent emerging and powerful models systems for high-throughput in vivo toxicity screening. These vertebrates present unique properties, including small size, high genetic homology to mammals, and optical transparency. This book chapter presents an overview of these models, in terms of exceptional peculiarities, and of the different types of parameters that can be assessed to investigate the potential toxic effects of nanomaterials at multiple levels. In addition, it highlights the toxicity screening of several classes of nanomaterials, including carbon-based nanomaterials, metallic nanoparticles, and semiconductor nanomaterials.