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Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the United States, and it accounts for approximately 500,000 hospitalizations for exacerbations each year. New definitions of acute COPD exacerbation have been suggested, but the one used by Anthonisen et al. is still widely accepted. It requires the presence of one or more of the following findings: increase in sputum purulence, increase in sputum volume, and worsening of dyspnea. Patients with COPD typically present with acute decompensation of their disease one to three times a year, and 3% to 16% of these will require hospital admission. Hospital mortality of these admissions ranges from 3% to 10% in severe COPD patients, and it is much higher for patients requiring ICU admission. The etiology of the exacerbations is mainly infectious (up to 80%). Other conditions such as heart failure, pulmonary embolism, nonpulmonary infections, and pneumothorax can mimic an acute exacerbation or possibly act as “triggers.” Baseline chest radiography and arterial blood gas analysis during an exacerbation are recommended. Oxygen administration through a venturi mask seems to be appropriate and safe, and the oxygen saturation should be kept just above 90%. Either a short acting β2-agonist or an anticholinergic is the preferred bronchodilator agent. The choice between the two depends largely on potential undesirable side effects and the patient's coexistent conditions. Adding a second bronchodilator to the first one does not seem to offer much benefit. The evidence suggests similar benefit of MDIs when compared with nebulized treatment for bronchodilator delivery. If MDIs are to be used, spacer devices are recommended. Steroids do improve several outcomes during an acute COPD exacerbation, and a 10- to 14-day course seems appropriate. Antibiotic use has been shown to be beneficial, especially for patients with severe exacerbation. Changes in bacteria strains have been documented during exacerbations, and newer generations of antibiotics might offer a better response rate. There is no role for mucolytic agents or chest physiotherapy in the acute exacerbation setting. Noninvasive positive pressure ventilation might benefit a group of patients with rapid decline in respiratory function and gas exchange. It has the potential to decrease the need for intubation and invasive mechanical ventilation and possibly decrease in-hospital mortality.