The pathology of fibrosis is defined by excessive accumulation of fibrous connective tissue components of the ECM (i.e., collagen and fibronectin) in inflamed tissue ( 11), which in iSGS leads to airway obstruction. Investigations have repeatedly demonstrated pathologic extracellular matrix (ECM) deposition in the subglottic lamina propria ( 8- 10). Likely as a consequence of the surgical approach to treatment, our understanding of iSGS has historically been based on histopathology. Alternatively, durable success with CTR is higher but is associated with greater postoperative phonatory disability ( 5, 7, 8). Endoscopic dilation is safe and effective but often only temporizing ( 1, 6). Surgical strategies for iSGS range from endoscopic interventions (focused in increasing airway diameter through dilation) ( 1) to open cricotracheal resection (CTR) ( 4, 5). Due to the progressive nature of this disease, surgical interventions aimed at increasing airway diameter are the primary treatment modality ( 3). Despite the initial clinical description of iSGS more than 40 years ago ( 2), the pathogenesis of this disease remains an enigma. Persistent mucosal inflammation and a localized fibrotic response are hallmarks of the disease. iSGS is clinically rare, almost exclusively affects Caucasian females between the ages of 40–60 years ( 1). It arises without known antecedent injury or associated disease process. Idiopathic subglottic stenosis (iSGS) is a debilitating extrathoracic obstruction involving the lower laryngeal and upper tracheal airway. Keywords: Idiopathic subglottic stenosis (iSGS) immunity interleukin-17A (IL-17A) transforming growth factor beta (TGF-β) While the role of the immune response as inciting event in iSGS remains unresolved, the centrality of an active immune response to the observed subglottic tissue remodeling is becoming more defined. Recent investigations focusing on the inflammatory response associated with iSGS have sought to characterize the immunophenotype and cytokine profile of the airway scar in iSGS. One of the most common is sustained host inflammation. Diverse diseases in divergent organ systems are associated with fibrosis, suggesting common pathogenic pathways. iSGS is a fibrotic disease marked histologically by excessive accumulation of fibrous connective tissue components of the extracellular matrix (ECM, i.e., collagen and fibronectin) in inflamed tissue, which leads to airway obstruction and clinical dyspnea. It arises without a known antecedent injury or associated disease process. Abstract: Idiopathic subglottic stenosis (iSGS) is a debilitating extrathoracic obstruction involving the lower laryngeal and upper tracheal airway.