Acute exacerbations of COPD (AECOPD) are major clinical events. They are associated with a more rapid decline in lung function, poorer quality of life scores, and an increased risk of dying. Exacerbations that require hospitalization have particular significance. Approximately 40% of the AECOPD patients who require hospitalization will die in the subsequent year. Since many AECOPD require hospitalization, they account for most of the expense of caring for COPD patients. Treatment with long-acting bronchodilators and combination inhaled corticosteroid/long-acting bronchodilator inhalers reduces but does not eliminate AECOPD. Roflumilast, a selective phosphodiesterase 4 (PDE4) inhibitor, is an anti-inflammatory medication that improves lung function in patients with COPD. In patients with more severe airway obstruction, clinical features of chronic bronchitis, and a history of AECOPD, roflumilast reduces the frequency of AECOPD when given in combination with short-acting bronchodilators, long-acting bronchodilators, or inhaled corticosteroids. It is generally well tolerated but the most common adverse effects include diarrhea, nausea, weight loss, and headaches. In clinical trials, patients treated with roflumilast experienced weight loss that averaged just over 2 kg but was primarily due to the loss of fat tissue. Weight loss was least in underweight patients and obese patients experienced the greatest weight loss. An unexpected benefit of treatment with roflumilast was that fasting blood glucose and hemoglobin A1c levels improved in patients with comorbid type 2 diabetes mellitus. Roflumilast, the first selective PDE4 inhibitor to be marketed, is a promising drug for the management of COPD patients with more severe disease.