As of January 2021, the U.S. Food and Drug Administration has approved four radiation exposure medical countermeasures (MCMs) to treat hematological acute effects, but no MCM is yet approved for radiation-induced lung injury (RILI). MCM approval for RILI and other subsyndromes utilizes the FDA Animal Efficacy Rule (Animal Rule), that requires demonstration of MCM efficacy in animal models with well-characterized pathophysiology, therefore, allowing translation to human use. A good animal model replicates the clinical condition and natural history of the disease, while allowing for studying the mechanism of action of the applied MCM and exhibiting clear benefits in terms of primary and secondary endpoints. However, there is much conversation regarding the advantages and limitations of individual models, and how to properly apply these models to demonstrate MCM efficacy. On March 20, 2019, the Radiation and Nuclear Countermeasures Program (RNCP) within the National Institute of Allergy and Infectious Diseases (NIAID), Food and Drug Administration (FDA), and the Biomedical Advanced Research and Development Authority (BARDA) sponsored a workshop to identify critical research gaps, discuss current clinical practices for different types of pulmonary diseases, and consider available animal models for RILI.