Domestic ferrets (Mustela putorius furo) have been used in biomedical research to study influenza viruses since the early 20th century. Ferrets have continued to gain importance for the study of viral respiratory disease due to their disease susceptibility and anatomic similarities to humans. Here we review features of ferret biology and management that should be considered when planning to work with this species, particularly in models of respiratory disease. We specifically discuss biosafety and husbandry, clinical and pathologic assessments, and anesthetic considerations for ferrets with respiratory disease and systemic illness. These considerations are important for animal welfare, fidelity of the model to human disease, and ensuring accuracy and reproducibility of acquired data. Finally, we briefly review the use of ferrets to study respiratory diseases by discussing their respiratory anatomy and 2 frequently studied viral respiratory diseases, influenza and coronavirus disease 2019 (COVID-19).