To review the safety and efficacy of minocycline 4% topical foam for the treatment of moderate to severe acne vulgaris in adults and pediatric patients aged 9 years and older. A literature search through PubMed and EMBASE was conducted using the following keywords: , , , and . Articles selected included those describing preclinical and clinical studies of pharmacokinetics, efficacy, or safety of topical minocycline foam. Minocycline 4% topical foam was shown in a preclinical study to effectively deliver minocycline to the pilosebaceous unit, with little penetration beyond the stratum corneum. This was consistent with a phase 1 pharmacokinetic study of the foam, which yielded a significantly reduced systemic exposure of minocycline compared with oral minocycline. In phase 2 and phase 3 clinical trials, the foam significantly reduced acne lesion counts and Investigator's Global Assessment scores of acne severity compared with placebo. The foam has a good safety profile, with headache, mild erythema, hyperpigmentation, and mild dryness among the most common adverse effects. Topical antibiotics have been a mainstay of acne therapy with the benefit of less systemic exposure compared with oral antibiotics. However, the development of bacterial resistance has reduced their use, thereby reducing options for many patients with acne. Minocycline 4% topical foam is a safe and effective alternative, which may help restore this important therapeutic approach for treating acne vulgaris.