Chronic obstructive pulmonary disease (COPD) is a chronic disorder whose clinical course may be punctuated by exacerbations characterized by a sudden symptom worsening beyond the expected daily variations. Exacerbations of COPD are of major importance because frequent episodes of exacerbations accelerate loss of lung function, affect the quality of life of the patients, and are associated with prognosis. It is thus important to prevent exacerbations in the management of COPD. In general, exacerbations become more frequent with increasing levels of obstructive impairment, but the single best predictor of the exacerbations is a previous history of exacerbation. The phenotypes susceptible to exacerbations, independent of degree of air-flow limitations or previous exacerbations, should be identified. COPD patients with the symptoms of persistent cough and sputum are known to be associated with frequent exacerbations. These patients are classified into the phenotype as chronic bronchitis, which has the persistence of an inflammatory process in the airways. Moreover, elevated levels of inflammatory biomarkers in patients with COPD are associated with a history of frequent exacerbations. It is suggested that the treatment targeting inflammation is very important to prevent exacerbations in COPD. Along with long-acting bronchodilators, anti-inflammatory agents, including phosphodieseterase (PDE) 4 inhibitors, macrolides, and mucolytics, are expected to prevent exacerbations. The new Spanish COPD Guideline has provided fresh insights into the management of the disease. It defines various disease phenotypes with different clinical, prognostic, and therapeutic implications. One of these phenotypes is the so-called “exacerbator,” characterized by a high incidence of exacerbations (two or more moderate-severe exacerbations in the past year). For those exacerbators in the phenotype of chronic bronchitis, anti-inflammatory agents, including PDE 4 inhibitors, would be a promising strategy for preventing exacerbations.