Chronic obstructive pulmonary disease (COPD) is the fourth most common cause of death worldwide. Recurrent acute exacerbation of COPD (AE-COPD) are common attributes of its course, and are related to the progress of the disease and its high cost. In the USA, that cost is estimated at $7,757 per exacerbation, mainly due to hospitalization expenses. Patients with repeated acute exacerbations rapidly display reduced lung function and they have a prolonged recovery time and an increased likelihood of suffering from depression or stress, which may consequently lead to a poorer quality of life. Given the fact that almost half of AE-COPD episodes are the outcome of infection, the administration of antimicrobial medication is recommended for patients suffering from exacerbations or severe COPD. In order to administer antibiotics correctly, the risk factors involved in the exacerbation and the choice of the appropriate antibiotics for patients of low and high risk should be taken into consideration. In accordance with the international guidelines, the prophylactic use of antibiotics for patients with COPD is not recommended, although ongoing clinical trials are reevaluating the administration of macrolides as a means of preventing exacerbations, based on their anti-inflammatory properties.