Introduction: Chronic rhinosinusitis (CRS) is a common upper airway disease with a prevalence of greater than 10% of the general population. Although the pathogenesis of CRS remains poorly understood, there is growing evidence indicating that epithelial physical barrier defects play an important role in CRS pathogenesis. Areas covered: Epithelial physical barriers are maintained by various intercellular junctions, especially tight junctions (TJs). Recent studies suggest that the expression of TJ molecules and epithelial barrier function in human nasal epithelium are modulated by various internal and external factors. This review summarizes recent advances regarding the structure, function, and regulating mechanisms of the epithelial physical barrier in the context of CRS. Expert opinion: Available data indicate that epithelial physical barrier defects in CRS can result from inhaled allergens, microbial or virus infections, cytokines, hypoxia, or zinc deficiency, among other causes. Several genes/molecules, such as SPINK5, S100A7, S100A8/9, PCDH1, NDRG1, SPRR, and p63 are involved in modulating the physical barrier function in the context of CRS. The exact mechanisms and molecular pathways that lead to these barrier defects, however, require additional study. Additional work is necessary to further explore the epithelial physical barrier function in normal and pathologic sinonasal mucosa.