BACKGROUND: Several options are available for the treatment of chronic rhinosinusitis (CRS), but disease control remains elusive for many patients. Recently, literature has emerged describing anti-IgE monoclonal antibody as a potential therapy for CRS. However, its effectiveness and safety are not well known. The purpose of this systematic review was to assess the effectiveness and safety of anti-IgE therapy and to identify evidence gaps that will guide future research for the management of CRS. METHODS: Methodology was registered with PROSPERO (No. CRD42014007600). A comprehensive search was performed of standard bibliographic databases, Google Scholar, and clinical trials registries. Only randomized controlled trials assessing anti-IgE therapy in adult patients for the treatment of CRS were included. Two independent reviewers extracted data using a pre-defined extraction form and performed quality assessment using the Cochrane risk of bias tool and the GRADE framework. RESULTS: Two studies met our inclusion criteria. When comparing anti-IgE therapy to placebo, there was a significant difference in Lund-McKay score (p = 0.04) while no difference was seen for percent opacification on computed tomography (CT). At 16 weeks, treatment led to a decrease in clinical polyp score. No significant difference was seen with regard to quality of life (Total Nasal Symptom Severity (TNSS), p < 0.21; Sinonasal Outcome Test 20 (SNOT-20), p < 0.60), and no serious complications were reported in either trial. Based on the quality assessment, studies were deemed to be of moderate risk of bias and a low overall quality of evidence. CONCLUSIONS: There is currently insufficient evidence to determine the effectiveness of anti-IgE monoclonal antibody therapy for the treatment of CRS.