Acute exacerbations of COPD are episodes of acute worsening during the course of COPD that are characterised by an increase in respiratory symptoms. Acute exacerbations are not benign, and are associated with significant morbidity and mortality—both in the short and long term. This chapter discusses the pathobiology of exacerbations, provides a rational approach for the evaluation of potential exacerbators, and examines the basis for the preventive therapy of exacerbations. Conditions that may present as exacerbations of COPD are also discussed in some detail.