Background Epithelial barrier disturbances in CRSwNP patients play an important role in both the innate and adaptive immune responses, contributing to chronic inflammation, olfactory dysfunction, and impairments in quality of life. Objective To evaluate the role of the sinonasal epithelium in disease and health, review the pathophysiology of epithelial barrier dysfunction in CRSwNP, and the immunologic targets for treatment. Methods Literature review. Results Blockade of cytokines such as thymic stromal lymphopoietin (TSLP), IL-4, and IL-13 have shown promise in barrier restoration and IL-13, specifically may be central to olfactory dysfunction. Conclusion The sinonasal epithelium plays a crucial role in the health and function of the mucosa and immune response. Increased understanding of the local immunologic dysfunction has led to several therapeutics that can potentially restore epithelial barrier function and olfaction. Real world and comparative effectiveness studies are needed.