Copyright © 2016 Journal of Drugs in Dermatology. All Rights Reserved. The use of Polypodium leucotomos, a species of fern, has been reported to be beneficial in the treatment of atopic dermatitis, vitiligo, and psoriasis, and for prevention of polymorphic light eruption, sunburn, and squamous cell carcinoma. We review the in vivo animal, in vitro human, and human clinical studies performed to help elucidate the actions of and biologic pathways affected by P. leucotomos. These results serve as the scientific rationale and basis for the protection and effectiveness afforded by P. leucotomos in cutaneous diseases.