Despite optimal use of currently available therapy for stable COPD, acute exacerbations are common events that constitute a major health burden. The development of highly sensitive diagnostic tools highlighted the role of viral infections in inducing COPD exacerbations, with rhinoviruses being the most frequently identified virus type. So far, little is known about the mechanisms of virus-induced exacerbations. The recent development of the first human rhinovirus-induced COPD exacerbation model represents an invaluable tool towards increasing our knowledge of immunological and inflammatory mechanisms of COPD exacerbation. The model will give us the opportunity to highlight key inflammatory mediators representing possible therapeutic targets for the development of novel drugs able to treat and prevent acute episodes in COPD.