Human and animal respiratory tract models are useful for investigating host responses to infection. Their scalability and physiological relevance to the in vivo respiratory tract make them ideal for studying respiratory pathogens rapidly and efficiently. They are also valuable for evaluating the efficacy of therapeutics. In our lab we have established a comprehensive in vitro respiratory tract platform that enables the study of infection in human nasal epithelial cells, large airway epithelial cells, small airway epithelial cells and alveolar type II cells. In addition, we are currently setting up complementary precision-cut lung slice models using mouse and ferret lungs to study infection in situ. To date, we have used these models to compare virus replication kinetics, cellular tropism and host response to seasonal and pathogenic coronaviruses (CoVs) across the respiratory tract with the aim to uncover virus-host interaction signatures associated with respiratory tract location and virus type. We have also used these models to isolate hard-to-recover contemporary seasonal CoVs from human clinical samples which can now be used to compare virus-host interactions to traditional laboratory seasonal CoV strains. In future, we plan to expand the use of these models to other respiratory viruses such as Influenza A viruses. Overall, the characterisation of virus-host interactions in physiologically relevant respiratory tract models will help us understand how to better prepare for the emergence of future novel viruses with pandemic potential.