This article synthesizes and appraises the methodological quality of the international literature on costs of chronic obstructive pulmonary disease (COPD) exacerbations, economic value of antimicrobial therapy of exacerbations, and factors affecting the economic value of antibiotics. Included studies had carried out a cost-of-illness, cost-effectiveness, cost-utility or cost-benefit analysis. Exacerbation costs varied between countries and increased with the severity of the exacerbation. Hospitalization costs accounted for more than 45% of healthcare costs of exacerbations. Drug costs made up 6-21% of healthcare costs in the majority of studies. Cost estimates were biased due to difficulties involved in diagnosing and treating exacerbations, and because the patient sample studied may not be representative of the population of patients suffering from exacerbations. Although this needs to be corroborated by future research, evidence is emerging that second-generation antibiotics such as fluoroquinolones may have a favourable economic profile as compared with first-generation antibiotics. The higher acquisition costs of fluoroquinolones appear to be balanced by less treatment failure, more time between exacerbation episodes, and lower hospitalization costs. There is a need for prospective economic evaluations alongside clinical trials with a sufficient number of patients and length of follow-up period. The economic value of antibiotics is influenced by difficulties involved in diagnosing the condition, effectiveness, resistance, patient compliance with treatment, and treatment failure associated with antibiotics. The small number of economic evaluations and their methodological Limitations precludes the recommendation of a specific antibiotic for use in the management of COPD exacerbations on economic grounds. (c) 2006 Elsevier Ltd. All rights reserved.