There is an urgent need to identify hazards posed by novel nanomaterials (NMs) however, new models are required to streamline testing approaches, increase our understanding of mechanism of toxicity and incorporate Safer-by-Design (SbD) concepts into NM development. Considering one of the main routes of exposure to NMs is via inhalation, the development of in vitro airway models has been a priority area of research in recent years. Over the last 20 years new models and methods have ranged from simple submerged co-cultures of prominent lung cell types to the development of organoids and organ-on-a-chip approaches that include the complex cellular interactions. Current and future efforts to construct more advanced models aim to better mimic the dynamic physiological features of the lung tissue including mechanosignalling from tissue stretching and the incorporation of fluid flow. In this chapter, we will discuss the development and application of advanced in vitro models for assessing NM inhalation hazard and the potential impact for promoting SbD in NM development.