Exacerbations of chronic obstructive pulmonary disease (COPD) have a profound effect on the patient's health status and decline in lung function; they also impose a significant burden on healthcare resource utilization. Prevention and treatment of exacerbations is listed by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) as among the major objectives of COPD management, and it is therefore an important outcome measure when studying any new agent. This article discusses pharmacologic therapy and other measures for preventing exacerbations and hospitalizations due to exacerbations of COPD.