Nanomaterials possess different properties that make them suitable for application in numerous fields. Nonetheless, their toxicity, especially their neurotoxic propensity, is a considerable area of investigation. In this chapter, nanomaterial neurotoxicity is reviewed in detail, with an emphasis on assessing toxicity, levels of exposure or routes of entry to brain cells, mechanisms by which they cause damage, and specific types of damage. In addition, in this chapter, in vitro, ex vivo, and in vivo models used to measure neurotoxicity are described. This chapter provides a discussion of this matter by considering challenges in terms of nanomaterial characterization, risk assessment, and regulatory aspects. This chapter concludes by underscoring the importance of toxicological models of prediction and safe-by-design solutions. Future research should address the long-term effects of using nanomaterials and the means of preventing their neurotoxicity.