COPD is one of the most common causes of morbidity and mortality. Perhaps paradoxically, COPD also should be an orphan disease. Importantly, this could advance the development of treatments for COPD. There are two criteria for orphan status in the United States. Most widely known is the criterion of < 200,000 affected individuals; however, secondarily, is the impossibility for development costs to be recovered during the patent life of a product. COPD should qualify for the first criterion if the various conditions that comprise COPD are regarded separately. The subphenotyping of COPD into separate groups based on mechanism sets the stage for the rational development of therapeutics. In addition, many candidate treatments may alter the natural history of COPD. Testing them, however, will require large studies for a duration that will compromise the commercial life of any resulting product. Orphan status, therefore, could facilitate the development of treatments for both phenotypic subsets of COPD patients as well as aid the development of agents to alter the natural history of the disease. Post-drug approval regulations could require that agents approved under the orphan provisions are prospectively monitored, assuring that rigorous longitudinal data are generated. This approach could encourage the pharmaceutical industry to stratify studies based on a more detailed characterization of study subjects at baseline, thus approaching “many small COPDs” instead of a single large and heterogeneous COPD. This strategy may help to address the increasing burden that COPD presents and for which no novel clinical class of treatment has been introduced for 30 years.