Chronic obstructive pulmonary disease (COPD) is increasing in prevalence. Acute exacerbations of COPD are the major cause worldwide of morbidity, mortality, and health care costs as well as decreased quality of life for the individual. The majority of exacerbations are infectious in etiology. Bacteria are detected in 50% of exacerbations and polymerase chain reaction techniques have established that, in half to two-thirds of exacerbations, viruses are causative pathogens. Combined bacterial and viral infection can be identified in 25% of exacerbations and these dual infections are often more severe. Despite occurring frequently, the mechanisms by which infection with these pathogens causes exacerbations are incompletely understood. This highlights the need for continued research, because a greater understanding of the mechanism of COPD exacerbations may lead to identification of potential targets for the development of therapeutic options for this increasingly common condition.