Exacerbations of chronic obstructive pulmonary disease (COPD) cause a lot of hospital admissions, mortality, and strongly influence health-related quality of life. Approximately half of COPD exacerbations are associated with bacterial infections and many patients have lower airways colonization. Current guidelines recommend antibotic therapy in course of COPD exacerbation for patients with sputum purulence and suggest correlation between severity of symptoms and the type of infecting pathogen. The most common bacterial pathogens isolated in COPD exacerbation are Haemophilus influenzae and parainfluenzae, Streptococcus pneumoniae and Moraxella catarrhalis. The presence of these bacteria are more common for mild and moderate exacerbations. More virulent organisms such as Staphylococcus aureus and Pseudomonas aeruginosa have been found in more severe cases. Atypical pathogens such Chlamydophila and Mycoplasma could cause exacerbation alone or they could coexist with typical pathogen. Rules of antibiotic therapy and usefulness of macrolides in treatment of COPD exacerbation has been described in the article.