Acute exacerbation of chronic bronchitis (AECB) is a condition associated with increased morbidity and mortality. Bacterial infections are the most frequent cause of exacerbations. The most common bacterial etiologies include Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumonia. The diagnosis of AECB is often based on the clinical presentation, but microbiological assessment, including Gram stain and sputum culture should be done. Antibiotic therapy should be used in patients with the following characteristics: underlying lung disease, frequent exacerbations, and comorbid conditions. Penicillins, erythromycin, beta-lactamase inhibitors, and trimethoprim-sulfamethoxazole have been the preferred antibiotics. However, because of the increasing prevalence of resistance among respiratory pathogens, mainly the production of beta-lactamase by H. influenzae and M. catarrhalis, and the emergence of multidrug-resistant S. pneumonia, new generation macrolides and fluoroquinolones should be the first line of treatment in selected patients. These drugs have increased efficacy and safety.