Recurrent respiratory papillomatosis is a rare but often severe disease. Although benign in histology, epithelial proliferations may result in progressive hoarseness, stridor, obstruction of the airway and respiratory distress. The current standard of care is surgical therapy with a goal of complete removal or debulking of papillomas and preservation of normal structures. Frequent recurrences and the need for repeated surgical interventions make this treatment a frustrating experience for both the patient and the physician. Many adjuvant therapies have been investigated but no single treatment modality proved to be effective in eradicating recurrent respiratory papillomatosis. In contrast to HIV, cytomegalovirus and hepatitis B pharmaceutical research has been less successful with human papilloma virus vaccines for a variety of reasons. This review focuses on the current status of recurrent respiratory papillomatosis and on future directions of prevention and therapy.