Recurrent Aphthous Stomatitis (RAS) is characterized by painful recurring ulceration of oral mucosa and is the most common oral ulcerative disease. The specific etiology of the disease remains unknown. This situation makes the therapy of RAS difficult and uncertain. This article will discuss the effectiveness and the safety of amlexanox 5% in relieving the symptoms and accelerate healing in RAS lesions. Amlexanox 5% is a new drug used topically in treatment of RAS. The mechanism of action by which amlexanox accelerates healing of RAS is unknown. Clinical study of efficacy amlexanox 5% has been demonstrated significantly accelerate healing and reduce pain of RAS, compared to amlexanox 1%, vehicle and no treatment. 5% amlexanox oral paste has an advantageous pharmacological activity to accelerate healing and reduce the pain of RAS, thus it can be used as one of the modality in this therapy.