Chronic Obstructive Pulmonary Disease (COPD) is characterized by irreversible airflow limitation. It is a global disease and expected to be the third leading cause of death. Respiratory exacerbations are associated with increased mortality and morbidity in this patient population. Respiratory viruses were isolated from at least 30 to 50% of the infectious respiratory COPD exacerbations with rhinovirus being most commonly isolated pathogen. Although rhinovirus does not cause airway epithelial damage like influenza and other respiratory viruses, it may further impair innate immunity of airway epithelium, which is the first line of defense in the lungs. This may increase susceptibility to secondary bacterial infections leading to progression of lung disease. Currently, there arc no therapies available to treat rhinovirus infection in COPD and therefore understanding the mechanisms underlying RV pathogenesis in COPD is essential to identify molecular target to develop new therapeutic strategies. Quercetin, a plant polyphenol, which modulates innate immunity and effectively blocks viral replication may be useful in treating rhinovirus associated COPD exacerbations.