Recurrent respiratory papillomatosis (RRP) is the most common benign pediatric laryngeal neoplasm. Various adjuvant medical therapies have failed to reliably decrease surgical frequency in this challenging airway disease. Recently, systemic bevacizumab has shown promise in advanced, treatment-resistant papillomatosis. We describe the use of systemic bevacizumab in two children with severe RRP unresponsive to other therapies. Voice and breathing improved dramatically in both patients with minimal side effects. Both patients have not required surgery in 23 months and 15 months, respectively. Systemic bevacizumab is a promising long-term treatment for severe RRP, with oncology playing an important role in patient care.