Chronic Rhinosinusitis (CRS) is a multifactorial disease, and different etiologies like metabolism and immunity disorders, bacterial superantigens, biofilms, and fungal allergens are known to develop this disease, especially the CRS with nasal polyps. Alternaria alternata (Alternaria) is one of the most prevalent airborne fungal species in the nasal discharge, which might have vigorous immunologic activities in nasal epithelial cells and play an essential role in the pathogenesis of CRS. Moreover, the interaction between this fungus and the innate and adaptive immune systems leads to the development of chronic inflammation. This inflammation may consequently instigate the CRS and nasal polyposis. The attenuation of surfactant protein synthesis or intracellular reserves and mucus hypersecretion could prevent the clearance of Alternaria from sinuses and may be correlated with colonization and re-infection of airborne fungi. Furthermore, higher expression of cathelicidin, thymic stromal lymphopoietin, toll-like receptors, and T helper 2-dominant immune responses can result in an IgE-mediated pathway activation and eosinophils degranulation. Moreover, higher local Alternaria-specific IgE was shown to be correlated with eosinophilic cationic proteins and might relate to nasal polyps. However, the role of genetic and environmental factors affecting CRS and nasal polyposis is not well studied. Likewise, further animal and clinical studies are required to better understand the role of Alternaria in CRS disease. The current article reviews the recent findings around the Alternaria-induced CRS and nasal polyposis.