Chronic rhinosinusitis (CRS) is characterized by persistent symptomatic inflammation of the nasal and paranasal sinus mucosa resulting from the interaction of multiple host and environmental factors. Although the etiology of CRS remains a matter of vigorous debate, research into CRS has implicated that the epithelium plays an important role as both a mediator and a regulator of innate and adaptive immune responses, as well as the transition from innate immunity to adaptive immunity. Recently, alterations of epithelial barrier functions, dysregulation of the innate immune system and inappropriate activation of the adaptive immune system have been identified as active processes in the pathogenesis of CRS. This review summarizes recent emerging evidence regarding the underlying pathogenic mechanism in CRS, which highlights the increasing recognition of the epithelium as a central factor in CRS etiology and pathogenesis.