In practice, antimicrobial treatment is usually thought to be regularly indicated in the treatment of patients with acute exacerbations of COPD. However, data supporting this practice are very limited. Most placebo-controlled studies do not satisfy currently required methodological quality standards. We develop a concept of restrictive indications for antimicrobial treatment from the available data. Cornerstones of this concept include the selection of treatment setting as well as the indication for antimicrobial treatment according to the severity of the acute exacerbation (not primarily of COPD) and to the type of exacerbation (Anthonisen type I). The selection of antimicrobial agents is based on an intraindividual rotation concept in order to limit antimicrobial selection pressure. The concept presented here can at the same time be used as a clinical guide as well as a framework for future studies dealing with currently unresolved issues.