Primary immunodeficiency diseases (PIDs) are uncommon in adults; however, immunoglobulin G subclass deficiency (IGGSCD) is often found in a subset of adult patients with chronic respiratory diseases. As quantitative laboratory tests are used to diagnose IGGSCD, the clinical significance of IGGSCD remains controversial. However, respiratory infection is a common presenting feature of IGGSCD, and respiratory complications are responsible for subsequent morbidities, such as severe asthma, bronchiectasis, chronic obstructive airway diseases, and mortality. This review summarizes the current epidemiological data for PIDs, focusing on IGGSCD in the adult population. In addition, the investigation, treatment, and management strategies are detailed, including distinct issues faced by patients with chronic airway disease and their physicians in the proper diagnosis and treatment of IGGSCD.