Chronic obstructive pulmonary disease (COPD) is a common chronic disease seen in smokers associated with poor functional status, quality of life, and morbidity and mortality from acute worsening of chronic symptoms, also called exacerbations. As a disease, the risk factors for COPD are well defined; however, there is room for innovation in identifying underlying biological processes, or “endotypes,” that lead to the emergence and/or progression of COPD. Identifying endotypes allows for more thorough understanding of the disease, may reveal the means of disease prevention, and may be leveraged in novel therapeutic approaches. In this review, we discuss the interface of viral infections with both cellular and epithelial immunity as a potential endotype of interest in COPD.