BACKGROUND: Recurrent respiratory papillomatosis (RRP) is a condition caused by human papilloma virus (HPV) infection. Curative treatments aren't identifiable, and conservative surgery is often the best option to preserve respiratory functions. To date monoclonal antibodies are considered to be a treatment choice with both good efficacy and safety profile. MATERIALS AND METHODS: A web-based search of MEDLINE/PubMed library from 2000 to 2024 of English-language papers was performed to identify articles by using "respiratory or laryngeal papillomatosis" and "HPV respiratory infection, papillomatosis treatment, papillomatosis vaccine immunization, papillomatosis systemic treatment". Furthermore, a manual screening of references from original articles was done to identify additional studies. We selected 34 articles. RESULTS: Since 2009, the systemic administration of Bevacizumab has been used to treat RRP not responding to surgical treatment. The efficacy of an anti-VEGF monoclonal antibody in RRP lesions can be related to their vascular nature. The major concern is the rebound papilloma growth within the cessation of treatment. An interesting solution could be the concomitant use of immunotherapy to both reduce the burden of residual disease and activate the immune system against the HPV-infected cells. CONCLUSIONS: Bevacizumab has a safe profile with a short-term local eradication of HPV. Further prospective research with long-term follow-up is needed to better define its safety and results against the disease recurrence. Considering the role of the anti-HPV vaccine, both, in the prophylaxis of the infection and in the adjuvant setting, the actual data underline the need for evaluation of its therapeutic efficacy for the management of RRP.