Introduction: Oral mucositis (OM) is a common toxicity of cytotoxic cancer regimens and remains one of the most painful, injurious, and treatment-disrupting side effects of radiation and ablative therapy. Despite its frequency and impact, approved definitive preventive or therapeutic options remain limited.

Areas covered: This review focuses on mechanistically active small molecules and biologicals that are under clinical development for the prevention of oral mucositis. The authors have excluded those compounds and devices for which their indication is limited to symptoms management.

Expert opinion: OM remains a significant unmet clinical need. The commercial opportunities for an effective treatment have been characterized as a global market of $1 billion (US). The formulations of drugs under development vary considerably but share some several commonalities in their development scheme. All new agents are given prophylactically and are being evaluated in patients treated with concomitant chemoradiation therapy for head and neck cancer. The primary efficacy outcome for most trials is dependent on the assessment of mucositis using the scoring scale established years ago by the World Health Organization. The development activity for OM is robust with a diverse range of agents. New drug applications for effective therapeutic options for OM should be ready for review within the next few years.