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ABSTRACTIntroductionTopical drug delivery is highly attractive and yet faces tissue barrier challenges. Different physical and chemical methods have been explored to facilitate topical drug delivery.Areas coveredAblative fractional laser (AFL) has been widely explored by the scientific community and dermatologists to facilitate topical drug delivery since its advent less than two decades ago. This review introduces the major efforts in exploration of AFL to facilitate transdermal, transungual, and transocular drug delivery in preclinical and clinical settings.Expert opinionMost of the preclinical and clinical studies find AFL to be safe and highly effective to facilitate topical drug delivery with little restriction on physicochemical properties of drugs. Clinical studies support AFL to enhance drug efficacy, shorten treatment time, reduce pain, improve cosmetic outcomes, reduce systemic drug exposure, and improve safety. Considering most of the clinical trials so far involved a small sample size and were in early phase, future trials will benefit from enrolling a large group of patients for thorough evaluation of the safety and efficacy of AFL-assisted topical drug delivery. The manufacturing of small and less costly AFL devices will also facilitate the translation of AFL-assisted topical drug delivery.