Exacerbations of chronic obstructive pulmonary disease (COPD) are a major cause of morbidity, mortality, and rising health care costs. In addition, they are associated with an accelerated loss of lung function and thus have a direct effect on disease progression. There are few studies examining the cellular and molecular mechanisms of COPD exacerbations. Exacerbations are linked to increased airway inflammation and oxidative stress, but many questions remain unanswered regarding the key inflammatory cells and mediators. Current therapies for COPD exacerbations are of limited effectiveness, and a better understanding of the inflammatory events at exacerbation is required to devise new therapeutic agents. The development of experimental models of exacerbation-for example, the use of experimental rhinovirus infection in humans with COPD-would greatly facilitate studies of exacerbations.