**Abstract**

This chapter focus on existing model systems used to evaluate the toxicity of nanoparticles. We will be discussing monolayer and 3D cell based toxicity models, In vivo models like rodents and zebrafish systems. A focus will also be given on ex vivo models like chick embryos. Each toxicity model system will be discussed with its advantages and limitations. The chapter will provide critical information to students and researchers studying nanotechnology about the potential systems to check the toxicity of the nanoparticles developed in the laboratory. This can be used as a quick guide to use a model system to check toxicity based on the different type of particle with informed decisions based on its advantages and disadvantages.

**Keywords:** nanoparticles, toxicity, in vitro assays, precision cut slice model, organ on a chip, *Drosophila melanogaster*, *Danio rerio*, non-human primates
