Coronavirus disease 2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been a rising international cause of morbidity and mortality. Angiotensin-converting enzyme 2 (ACE2) is identified as a key cell entry receptor for SARS-CoV-2 and suggested to be a limiting factor for viral entry at the initial infection stage. Recent studies have demonstrated that ACE2 expression is highly enriched in nasal epithelial cells and type II alveolar epithelial cells, highlighting the importance of respiratory tract as the primary target site of SARS-CoV-2. The expression of ACE2 in airway epithelial cells is tightly regulated by inflammatory milieu and environmental and internal stimuli. Very recently, ACE2 has been reported to have different expression levels in airways under distinct chronic inflammatory airway diseases, such as chronic obstructive pulmonary disease (COPD) and allergic asthma, which may associate with the COVID-19 risk and affect the management of primary airway diseases. In this review, we focus on the cutting-edge progress in distribution, expression, and regulation of ACE2 in respiratory system in physiological and pathological conditions, and their implication for the development of COVID-19. We also discuss the management of airway diseases, including asthma, COPD, allergic rhinitis, and rhinosinusitis in the era of COVID-19.