Recurrent aphthous ulcer (RAU) is the most prevalent oral mucosal disease in humans, estimated to affect between 5% and 50% of the general population. The minor manifestation of the condition is the most common and is characterised by small, shallow, round or oval lesions that are surrounded by a raised erythematous halo and are covered by a grey-white pseudomembrane. Appropriate management of patients with this condition is largely symptomatic and should focus on reducing ulcer duration, relieving pain and reducing or preventing ulcer recurrence. Amlexanox is a novel anti-inflammatory and anti-allergic agent that has been evaluated for the treatment of RAU in a series of robust clinical trials. After a 100mg dose of 5% amlexanox topical paste, applied directly to the lesion, the maximum serum concentration of the drug was 120 ng/mL, which was achieved 2.4 hours after application. Steady-state concentrations were achieved within 1 week of starting four times daily dosing and there was no evidence of accumulation. In terms of efficacy, application of 5% amlexanox topical paste was shown to consistently and significantly accelerate complete ulcer healing and the time to resolution of pain across four large efficacy studies. Significantly more patients had completely healed ulcers from day 3 (compared with no treatment) and day 4 (compared with vehicle). Healing was mirrored by an improvement in pain: significantly more patients had complete resolution of pain from day 2 (compared with no treatment) and day 3 (compared with vehicle). Overall, amlexanox was well tolerated, with a low frequency of adverse effects. In the oral application studies, adverse effects that were considered by investigators to be potentially related to the study treatment occurred in 2.4% and 2.1% of 5% amlexanox and vehicle recipients, respectively. These effects were mainly local and were all classed as mild to moderate in severity, with the exception of one case of severe stinging in the vehicle treatment group. Furthermore, the incidence of dermal irritation and sensitisation was very low with amlexanox. These findings suggest that 5% amlexanox topical paste is a useful and well tolerated therapeutic option for the treatment of RAU.