Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease characterized by a non-reversible limitation of expiratory airflow. In patients with COPD, distal airways are the major site of obstruction; early in the course of the disease, they show signs of being remodeled, inflamed, and/or obliterated. Recent technological advances, particularly in imaging and transcriptomics, have provided new information on this key area of the lung. The objective of this review is to provide an updated overall vision of knowledge on distal airways and how they are damaged in COPD.