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Introduction: The treatment of vitiligo is a persistent challenge in dermatology. New treatments are being offered and studied in this field for those resistant to or intolerant of classical therapies.Methods: In this systematic review, we study the use of prostaglandin analogues (PGAs) and phosphodiesterase inhibitors (PDEIs) in the treatment of vitiligo, as they are known for their pigmentation inducing effects through activating melanocytes. Methods: We searched four main online databases with the keywords “Vitiligo”, “Prostaglandin analogue” and “Phosphodiesterase inhibitor”.Results: A total of 42 articles were included, with 1027 cases, studying drugs like Bimatoprost, Latanoprost, Travoprost, Dinoprostone, Apremilast, Crisaborole, etc. Among the included studies, the treatment regimens are commonly once or twice daily for 12 to 48 weeks, with a mean of 20.61 weeks, and the routes of administration are mainly topical gels or ophthalmic solutions and oral tablets. Side effects are mild and tolerable, namely erythema, itching or burning sensations at application site for topicals, or gastrointestinal problems with Apremilast. Repigmentation results are significant in both adult and pediatric patients and progressive or stable vitiligo. PGAs and PDEIs outperform many classical therapies, e.g., narrowband ultraviolet B phototherapy (NB-UVB), tacrolimus, mometasone or methylprednisolone mini-pulse. PGAs or PDEIs are usually used in combination therapies to either cause synergism or increase drug delivery, and almost always enhance repigmentation, e.g., with NB-UVB, fractional CO2 laser, microneedling and mometasone.Conclusion: Monotherapy or add-on PGAs and PDEIs can be considered effective treatments for vitiligo and promising last resorts for those resistant to other therapies.Keywords: Vitiligo, Resistant vitiligo, Prostaglandin analogue, Phosphodiesterase inhibitor, Adult, Pediatric
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