Chronic obstructive pulmonary disease (COPD) exacerbations are common events that punctuate the natural history of COPD contributing to disease severity progression and being the major cause of COPD-related morbidity and mortality. Currently available pharmacological strategies are only partially effective at reducing or preventing COPD exacerbations. Viral infections are the most frequent cause of COPD exacerbations. The recent development of a human experimental model of rhinovirus-induced COPD exacerbations represents an innovative tool with the potential to increase our understanding of the inflammatory and immunological mechanisms that lead COPD patients to exacerbate after respiratory virus infections. Moreover this model will provide the opportunity to test, in a carefully controlled setting, novel pharmacological compounds with a potential for treating and preventing COPD exacerbations. In this chapter we will focus on the role of viral infections in COPD exacerbations and will discuss preliminary reports regarding the development of this human model of virus-induced COPD exacerbation.