Fungal species have been implicated in the pathophysiology of chronic rhinosinusitis (CRS). Based on this observation, some clinicians have employed topical antifungal therapy with amphotericin B (AMB); however, its efficacy has not been consistently supported by the literature.A comprehensive review of the English-language literature on the role of topical AMB therapy in CRS treatment was performed. Search criteria included placebo-controlled trials between the years of 2000 and 2009. Studies that reported outcomes based on computed tomography (CT), nasal endoscopy (NE), and symptom scores (SS) were included.Three published studies reported CT outcomes. After pooling patients from these 3 studies, meta-analysis revealed no significant difference between AMB-treated and control groups (p = 0.07). Four studies reported NE outcomes, in which central tendency (mean or median) and variance were identified. Among these 4 studies, combining AMB-treated patients did not reveal any significant effect when compared to the small control group (p = 0.53). Only 2 studies reported SS; no significant differences in symptoms were noted (p = 0.33).A systematic review of the literature does not support the use of topical AMB for the treatment of CRS.