The immune response to virus infection in the respiratory tract must be carefully balanced to achieve pathogen clearance without excessive immunopathology. For chronic respiratory diseases where there is ongoing inflammation, such as in asthma and COPD, airway immune balance is perturbed, and viral infection frequently worsens (exacerbates) these conditions. Reactive oxygen species (ROS) are critical to the induction and propagation of inflammation, and when appropriately regulated, ROS are vital cell signalling molecules and contribute to innate immunity. However, extended periods of high ROS concentration can cause excessive cellular damage that dysregulates antiviral immunity and promotes inflammation. Traditional antioxidant therapeutics have had limited success treating inflammatory diseases such as viral exacerbations of asthma or COPD, owing to nonspecific pharmacology and poorly understood pharmacokinetic properties. These drawbacks could be addressed with novel drug delivery technologies and pharmacological agents. This review summarises current research on ROS imbalances during virus infection, discusses the commercially available mitochondrial antioxidant drugs that have progressed to clinical trial and assesses novel drug delivery approaches for antioxidant delivery to the airways. Additionally, it provides a perspective on future research into pharmacological targeting of ROS for the treatment of respiratory virus infection and disease.