1. Photodynamic therapy is an established modality for the treatment of solid tumours and other accessible lesions. Although the concept and practice of combining light with a photosensitizing agent for the treatment of disease states has been around for almost a century, the understanding of the art and science therein has been tremendously enhanced over the past few years. 2. Photosensitized reactions are dependent on the generation of reactive oxygen species, in particular singlet oxygen, which accounts for the damaging effects on biological macromolecules, such as membrane lipids and proteins. Therefore, compounds that give a good yield of (1)O(2) are used as photosensitizers. 3. The main photosensitizers used in the clinical setting belong to the photofrin family; however, newer and more effective sensitizers are being evaluated for their potential clinical effectiveness. 4. Light sources have moved from the use of white light with specific filters in the old days to the more recent use of monochromatic light sources, such as lasers, to more sophisticated light-emitting diodes. However, dosimetry remains a big issue mainly because of difficulties in establishing the optimum treatment conditions for an approach that requires the fine-tuning of several variables, such as sensitizer and light doses and drug-to-light interval, as well as the issues of skin photosensitivity and low selectivity. A newer development to circumvent these and provide a broader application for this concept has been the phenomenon of photo-activation, whereby photo-exposure of chromophores to generate novel, small biologically active compounds has been demonstrated successfully. 5. The aim of the present review was to provide a general overview of the art and science of photodynamic therapy and to highlight some of the issues and recent developments in further advancing this modality of treatment.