Adult volunteer challenge models are commonly used in a number of infectious diseases, to demonstrate proof of concept for vaccines and large and small molecules. For respiratory virus pathogens, infections are deliberately induced under carefully controlled and monitored conditions, involving attenuated virus strains. For respiratory virus drug candidates, human challenge models present opportunity to support dose selection for continued development with opportunity for lower operational, cost and scientific challenges imposed by patient studies involving natural infection. The application of quantitative pharmacology affords opportunity in the optimal design and application of human challenge models to enhance drug development for respiratory viruses. Case examples of the application of quantitative pharmacology approaches support the application of human challenge models will be presented for both influenza and respiratory syncytial virus.