AIMS: To define the role of medical or surgical treatment in patients with periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA syndrome). METHODS: A Medline search was performed using the terms PFAPA, periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis, treatment. A systematic review of the English literature was performed. Papers on pyrexia of unknown origin in the pediatric population were excluded; this was because the clinical entities included in the differential diagnosis of pyrexia of unknown origin share many clinical characteristics with PFAPA, and may be ill defined. RESULTS: Twenty-seven papers have been published since 1989, of which 20 were in English language. There were five single case reports and two papers involving two patients each. There were 6 retrospective reviews of case notes, involving 5-94 patients over a 3-10 year review period. Given that current evidence on the effectiveness of tonsillectomy in PFAPA is extremely weak (level of evidence V), tonsillectomy should not be performed. CONCLUSIONS: PFAPA usually resolves without any long-term adverse effect, and as such, there is no role for tonsillectomy in these patients.