The small airways are located at the interface between alveoli and conducting airways. Airway epithelial cells form a continuous lining in the airways. They play a unique role as a protective physical and functional barrier to external deleterious agents. Human small airway epithelial cells (SAEpiC) regulate the immune responses by contributing to host defense through both; chemokine production and adhesion molecule expression. They also produce liquids contributing to pulmonary fluid balance. Many airway diseases, such as asthma, bronchiolitis, chronic obstructive pulmonary disease, and cystic fibrosis, involve damage to the airway surface epithelium. The study of human SAEpiC may help to identify new therapeutic options for preventing airway disorders. HSAEpiCare also useful tools to stablish in vitro disease models for High Throughput and High Content Screening.