The role of antibiotics in acute exacerbations of chronic bronchitis (AECB) remains controversial because patients commonly harbor the same bacteria in their sputum at times of stability and at times of acute illness. However, prospective randomized controlled trials do show a benefit for the use of antibiotics, compared with placebo, in AECB, particularly if patients have at least 2 of the following 3 symptoms: increased dyspnea, increased sputum volume, increased sputum purulence. In this setting, antibiotics have value, leading to a more rapid resolution of symptoms and a more rapid return of peak flow rate, compared with placebo. In addition, antibiotics may prevent some patients from developing secondary pneumonia and may prolong the time between exacerbations. When antibiotics are used, a variety of factors must be considered in choosing an agent. These include the likelihood of antibiotic-resistant bacteria, a factor that relates to defining subsets of patients. Patients can fall into 1 of 3 categories, each with a different suggested therapy. These categories include simple AECB, complicated AECB, and AECB at risk for infection with P. aeruginosa. In addition, an antibiotic should be chosen with pharmacokinetics and pharmacodynamic behavior in mind. In the future, research will need to confirm that careful selection of specific agents for specific patients can lead to improved patient outcomes, but already some preliminary data are supporting this concept.