Chronic obstructive pulmonary disease (COPD) comprises a spectrum of conditions including chronic bronchitis, emphysema, asthma, and bronchiectasis. It has a prevalence in the United States of 5.1% to 5.4% in the middle-aged to elderly population, with a lower rate in nonsmoking individuals. Moreover, COPD is complicated by frequent and recurring acute exacerbations of chronic bronchitis (AECB). Overall, COPD represents the fourth leading cause of mortality in the United States and is the second leading cause of work disability. This condition is also associated with high morbidity and health care expenditures. Despite the controversy over the need to prescribe antibiotics for patients with AECB, high-risk patients have been identified who will benefit from this therapy.These include, patients with a history of repeated infections (>4 per year), comorbid illnesses (such as diabetes, asthma, coronary heart disease), or marked airway obstruction. Furthermore, a bacterial cause is shown in approximately 50% of AECB episodes, and primarily includes Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae. Additionally, resistance among community-acquired respiratory pathogens in the United States has risen dramatically, with beta-lactamase production evident in 40% of H. influenzae and greater than 95% of M. catarrhalis isolates, and with approximately 10% of pneumococci highly resistant to penicillin and simultaneously resistant to macrolide antibiotics. The criteria used to make choices for antibiotic use in patients with AECB should include knowledge of the frequencies of pathogen resistance and patients' clinical characteristics. An effective antibiotic, however, must be able to rapidly resolve the acute infection with the least patient morbidity and need for hospitalization. Although there remains controversy as to when to initiate antibiotic therapy in patients with AECB, several guidelines have been published.