Despite significant advances in early diagnosis and treatment, skin cancer is one of the leading causes of death. Photodynamic therapy (PDT) is a new therapeutic modality that is emerging as an important resource against malignant tumors. This strategy is based on the action of photosensitizers, i.e. of molecules which may accumulate preferentially inside tumor cells where they exert a cytotoxic effect after excitation by light at appropriate wavelengths. Some forms of skin cancers and also some non-tumor pathologies are now treated with PDT. Several compounds with photosensitizing activity have been identified, and some of these molecules are commercially available. Many photoactive principles are natural compounds. Numerous reviews in the last decade have focused on photodynamic therapy, its effects and applications, but less attention has been paid to plant extracts or molecules of natural origin studied for their phototoxic activity to date.This review critically examines the potential role of various plant extracts and naturally occurring compounds in the treatment of skin cancer. Both in vitro and in vivo effects of these agents, together with their known related cellular and molecular mechanisms, are presented and discussed.