Photosensitizing drugs have been known and applied in medicine for several thousand years. However, the scientific basis for such use was vague or non-existent before about 1900. Photodynamic therapy, PDT, has now become an established treatment modality for several medical indications. Notably, in the cases of skin actinic keratosis, several forms of cancer and blindness due to age-related macular degeneration, PDT has been successful. PDT is the combined application of a lesion-localizing photosensitizer and light. PDT with porphyrin derivatives as photosensitizing drugs was developed from about 1960. The basic, underlying mechanisms for tumour localization of photosensitizers and processes explaining the effect of PDT on tumours were elucidated from about that time. It has become clear that PDT is efficient only in the presence of oxygen, and that the oxygen dependency of PDT is similar to that of X-rays. Singlet oxygen, 1O2, a short-lived product of the reaction between an excited sensitizer molecule and oxygen, plays a key role. In contrast to radiation therapy and chemotherapy, PDT has a low mutagenic potential and, except for skin phototoxicity, few adverse effects. Approvals for clinical use of PDT now exist in many countries. The annual number of scientific articles on PDT, clinical as well as basic, steadily increases and new aspects and applications of it continue to be discovered. Many of the new investigators are obviously not aware of the early work in the field and repeat many of the experiments that had been reported before the Internet and modern data bases were established. Therefore, in the present historical review, the early work is weighted more heavily than recent work that is more easily accessible to the readers.