Chronic rhinosinusitis (CRS) is a chronic disease that affects 14.2% of the US adult population. Despite being widespread, little is known about the etiology of CRS. Treatment has been symptomatic and focused on relieving symptoms. Recent investigations into causes of CRS have revealed that most CRS patients have an eosinophilic infiltration of their nasal tissue (mucosa), regardless of atopy and elevated immunoglobulin E levels. Although fungi are ubiquitous and in the nasal mucus of both healthy people and patients, it is only in the patients that the eosinophils (part of the inflammatory response) are found. Fungi in the nasal mucus are harmless, yet in CRS patients these same fungi stimulate an inflammatory response, inducing the eosinophils to leave the blood vessels and enter the nasal and sinus tissue and ultimately enter the nasal airway mucus. In the nasal mucus these eosinophils attack the fungi and destroy the fungi by the release of a toxic substance called major basic protein (MBP) from the granules in the eosinophils. This degranulation and release of the toxic MBP not only destroys fungi, but also produces collateral damage injuring the nasal and sinus mucosal lining tissue. The injury to the mucosal lining makes the nasal and sinus mucosa susceptible to penetration and potential infection by bacteria. When this tissue inflammation and damage is persistent and prolonged we call it CRS. The diagnosis of CRS is based largely on symptomatic criteria, with anterior rhinoscopy or endoscopy, and, if there is any doubt about the diagnosis, computed tomography imaging is employed to confirm the presence of diseased sinus mucosa. Treatment of CRS, whether medical (intranasal corticosteroids, saline irrigations) or surgical, is aimed at decreasing inflammation and obstruction in the sinonasal passages. Antibiotics, although commonly used in CRS, should not be administered unless there is suspicion of an acute bacterial infection. The theory behind the fungal and eosinophilic etiology of CRS has led to use of an antifungal compound, intranasal Amphotericin B. In clinical studies, topical irrigation with Amphotericin B has been shown to be both a safe and effective treatment for CRS.