Perioral dermatitis presents as an eruption of erythematous papules, pustules and papulovesicles, most frequently seen in young women. Oral tetracyclines have been considered the first line treatment for years. However, recent publications have found newer agents to be efficacious. The authors performed a review of the available data in order to determine the strength of evidence supporting published therapies. A Pubmed and Cochrane Library database search for all cases, case series, and clinical trials dealing with the treatment of perioral dermatitis in English. Most cases of perioral dermatitis are self-limited, if the possible exacerbants of cosmetics and topical corticosteroids are discontinued ("zero therapy"). Many trials support the use of oral tetracyclines as a first line medication, as it significantly shortens the time to papule resolution. Topical erythromycin also reduces the time to resolution, but not as quickly. Topical pimecrolimus does not appear to decrease the time to complete resolution, but it does rapidly reduce the severity of the disease, particularly if prior corticosteroid use has occurred. The evidence supporting topical metronidazole, which is frequently used to treat perioral dermatitis in children, is relatively weak and supported only by case series and a trial showing it to be inferior to tetracycline. The evidence most strongly supports the efficacy of zero therapy, topical pimecrolimus, oral tetracycline, and topical erythromycin.