Exacerbations of chronic obstructive pulmonary disease (COPD) are a major health problem, causing more than half a million hospital admissions per year in the United States. Although overall mortality is low, it is substantially higher with severe exacerbations that require intensive care and mechanical ventilation. The majority of COPD exacerbations result from infection, with typical bacterial organisms most commonly identified. Numerous randomized controlled trials and meta-analyses have documented the benefits of antibiotics, low-flow oxygen, and systemic corticosteroids, and the therapeutic equivalency of the major classes of bronchodilators (short-acting beta-agonist and anticholinergics). Randomized controlled trials also demonstrate that noninvasive ventilation can decrease the incidence of intubation, shorten stay, reduce infectious complications, and improve survival. Although patients who require intubation have the worst prognosis, the vast majority of them can be successfully liberated from mechanical ventilation. For invasively ventilated patients the clinical emphasis should be on improving patient-ventilator interaction and avoiding dynamic hyperinflation (intrinsic positive end-expiratory pressure).