Exacerbations, characterized by an increase in patients' symptoms above baseline, are characteristic of both chronic obstructive pulmonary disease (COPD) and asthma. Prevention of exacerbations and their expedient treatment are major goals for reducing the morbidity and cost of both conditions. Exacerbations, however, may also adversely affect the natural history of these disorders, perhaps by contributing to increased rates of lung function decline, systemic effects, and premature mortality. Although the available information is limited, the course of COPD is affected adversely by exacerbations in multiple ways. First, exacerbations likely lead to structural alterations in the lung and to permanently worsened airflow. Second, health status is adversely affected by exacerbations, and although the mechanisms are unclear, the effects are long lasting and may be irreversible. Less is known in asthma about the effect of exacerbations on natural history, but many of the same pathogenetic processes involved in COPD exacerbations likely play a role in some subjects with asthma as well. Future studies of how exacerbation affects the "natural history" of asthma and COPD will require a better understanding of the heterogeneity of exacerbations but promises to identify new therapeutic strategies to treat these disorders.