BACKGROUND: Thirty to 40% of patients using topical treatments do not comply with their treatment regimen. OBJECTIVE: To examine how tolerability is assessed, tolerability ratings, and clinical significance of tolerability ratings of topical antimicrobials for acne. METHODS: A literature search was performed using the terms "tolerability AND acne AND (benzoyl peroxide OR antimicrobial OR clindamycin OR erythromycin OR dapsone OR sulfur OR sulfacetamide)." Inclusion criteria were: 1) evaluation of tolerability, 2) use of an identified topical antimicrobial for acne treatment without combination retinoid use, 3) an original study, in English. RESULTS: Thirty-four of 132 articles met the inclusion criteria. Tolerability was measured through subject and investigator assessment of specific tolerability parameters and by reporting of adverse events. Nearly all of the acne treatments were well tolerated. Treatment related study discontinuation rates were low and had little to no relation to the degree of tolerability measures. LIMITATIONS: Patients may be more adherent in clinical trials than in clinical practice. Differences in the measure used to assess tolerability make comparisons difficult. CONCLUSIONS: Topical antimicrobial acne therapy is generally well tolerated. Discontinuation rates are low under study conditions. Tolerability of topical antimicrobial therapy for acne may not have great clinical significance.