BACKGROUND Impetigo is a common clinical problem seen in general practice. Uncertainty exists as to the most effective treatment, or indeed if treatment is necessary. OBJECTIVE To determine the most effective treatment for impetigo in a systemically well patient. METHODS Systematic review and meta-analysis. METHODS Databases were searched for relevant studies. The Cochrane highly sensitive randomised controlled trial (RCT) search string was employed and combined with the word 'impetigo' as the MeSH term and keyword. The bibliographies of relevant articles were searched for additional references. RCTs that were either double- or observer-blind, and involved systemically well patients of any age in either primary or secondary care settings, were included. Studies that selected patients on the basis of skin swab results were excluded, as were studies that were not in English. Cure or improvement of impetigo reported at seven to 14 days from start of treatment was the primary outcome measure. Meta-analysis was performed on homogeneous studies. RESULTS Three hundred and fifty-nine studies were identified, of which 16 met the inclusion criteria. Meta-analysis demonstrated that topical antibiotics are more effective than placebo (odds ratio [OR] = 2.69, 95% confidence interval [CI] = 1.49 to 4.86). There is weak evidence for the superiority of topical antibiotics over some oral antibiotics, such as erythromycin (OR = 0.48, 95% CI = 0.23 to 1.00). There is no significant difference between the effects of mupirocin and fusidic acid (OR = 1.76, 95% CI = 0.77 to 4.03). CONCLUSIONS This review found limited high-quality evidence to inform the treatment of impetigo. From that which is available, we would recommend the use of a topical antibiotic for a period of seven days in a systemically well patient with limited disease. Further research is needed on the role of flucloxacillin and non-antibiotic treatments for impetigo.