Chronic obstructive pulmonary disease (COPD) affects 15 million people and is the fourth leading cause of death in the United States. It places a considerable burden on the healthcare system, with exacerbations contributing to a significant proportion of this burden. Patients with recurrent exacerbation, who experience more than 2 exacerbations per year, are especially difficult to manage. Several potential host, pathogen, and treatment factors can be identified that contribute to recurrent exacerbation. Patients with recurrent exacerbations are often exposed to frequent courses of antimicrobials. Therefore, antimicrobial resistance among common bacterial pathogens is likely to be prevalent in this group of patients, and further complicates therapy in this already difficult-to-treat patient population. In the management of patients with recurrent exacerbation, one goal should be to decrease the frequency of exacerbations, for which several strategies are suggested. In this article, we will review available literature identified through an extensive search of Medline and PubMed on the characteristics and approach to management of these difficult-to-treat patients. There is a substantial need for more research to understand the etiology and identify efficacious interventions to reduce the frequency of exacerbations of COPD.