Acute exacerbations of chronic bronchitis (AECB) is an important cause of death and morbidity in developed countries and also has significant economic impact. The disease is characterized by increased dyspnoea, sputum volume and sputum purulence; the most commonly associated pathogens are Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis. H. influenzae and S. pneumoniae express virulence determinants that directly and indirectly impair mucociliary clearance and incite other consequences that are permissive to microbial persistence. Regarding the use of antibiotics, there is currently a lack of large-scale clinical trials that are sufficiently powerful to provide good evidence-based information. Nonetheless, antimicrobial chemotherapy has repeatedly been shown to confer benefit in patients with moderately severe features of AECB. Simple clinical criteria can be used to identify patients in whom there is a higher likelihood of treatment failure or mortality during AECB. These include significant cardiopulmonary co-morbidity, frequent exacerbations, advanced decline in lung function, malnutrition or other generalized debility, advanced age (>70 years) and concurrent treatment with corticosteroids. In such patients, an aggressive antimicrobial approach to AECB may be warranted in order to prevent clinical failure or representation. From a clinical perspective, appropriate drugs include those that are stable to beta-lactamases, are bactericidal against causative pathogens, penetrate diseased lung tissue in high concentrations and have a good safety profile.