Asthma and chronic obstructive pulmonary disease (COPD) are chronic inflammatory disorders of the respiratory tract that are characterized by airflow limitation. They are distinct conditions with different causes, structural changes, and immunopathology. The pathophysiology in asthma and COPD involves not only the proximal large airways, but also the distal small airways, and thus the small airways are an important therapeutic target in the treatment of both diseases. The assessment of diseased distal small airways is challenging. Extensive disease can be present in the small airways with little abnormality in conventional pulmonary function tests. Recent advances in imaging technologies have led to better spatial resolution to assess small airways morphology non-invasively. New physiological tests have been developed to detect disease and response to therapy in regional airways. Improving the efficiency of existing aerosolized therapy to direct drug to the appropriate lung regions may improve clinical efficacy. Approaches to target distal lung regions include developing new drug formulations with smaller aerosol particle size or using inhaler devices that emit aerosolized drug at slow inhalation flows. Large studies are needed to determine whether better distal lung deposition leads to improvements in small airways function that are translated into clinically significant patient outcomes.