Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the USA and currently there are minimal therapies specific for the treatment of COPD. To advance our knowledge on COPD pathogenesis and develop new therapeutics, animal models are needed that represent key clinical and pathologic features of the human disease. The primary animal models utilized to study COPD rely on several factors associated with disease progression, i.e. genetic and epigenetic changes, environmental exposures and the microbial flora of the lungs. Here, a systematic approach was taken to summarize and evaluate the current animal models employed to study COPD pathogenesis, comorbidities and exacerbations. The strengths and limitations of these disease models are also delineated. The rodent COPD models have been extensively utilized but several studies have highlighted the potential of larger animals as an additional approach. Due to the inherent heterogeneity of COPD, the usefulness of certain animal models may be limiting but still represent helpful means to explore gene functional studies, testing new therapeutics and the exploring the significance of microbial floral changes. Therefore, interpreting the findings from animal models for the study of COPD represents a critical approach in deciding possible future human therapeutics.

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