A number of well-designed comparison studies have shown the superiority of oral or injectable antibiotics over typical treatment in the treatment of impetigo contagiosa. Erythromycin, phenoxymethyl penicillin, intramuscular benzathine penicillin G as well as clindamycin, cefaclor and amoxicillin with clavulanic acid have been shown to be extremely effective. Because of significant differences in study design, it is difficult to compare drugs investigated in different studies. Intramuscular benzathine penicillin G consistently has been associated with the highest cure rates, especially in studies specifically of streptococcal impetigo. It is unclear whether these high cure rates reflect superior efficacy or are the result of lesser compliance with oral medication, but the latter explanation is quite likely. This information generally translates into daily practice as a recommendation of a penicillin or an erythromycin preparation for streptococcal impetigo unless the lesions are small and few in number, in which case topical therapy is probably sufficient. If oral antibiotics are prescribed they should be given for 10 days. Systemic as opposed to topical antibiotics should be considered more strongly in situations where the incidence of impetigo is high, since these drugs are clearly superior in sterilizing the lesions quickly to prevent transmission. Other situations that favor the use of systemic as opposed to topical antibiotics include the presence of nephritogenic strains in the population, whether endemic or epidemic, more severe or spreading lesions and a population with poor hygiene.