Objective: The aim was to systematically review the efficacy of photodynamic therapy (PDT) in the management of oral premalignant lesions. Methods: The addressed focused question was "Is PDT effective in the management of oral premalignant lesions?" PubMed/Medline, Google-Scholar, EMBASE and ISI Web of Knowledge databases were searched from 1984 till June 2014 using different combinations of the following keywords: photodynamic therapy; oral premalignant lesions; leukoplakia; erythroplakia; erythroleukoplakia; verrucous hyperplasia; and submucous fibrosis. Review articles, experimental studies, case-reports, commentaries, letters to the Editor, unpublished articles and articles published in languages other than English were not sought. The pattern of the present study was customized to mainly summarize the relevant information.Results: Thirteen studies were included. In these studies, the number of patients ranged between 5 patients and 147 individuals with mean ages ranging between 51 years and 62.2 years. Oral premalignant lesions which were investigated were leukoplakia, erythroplakia, erythro-leukoplakia and verrucous hyperplasia. Reported number of premalignant lesions ranged between 5 and 225. Laser wavelength, duration of irradiation and power density were 585-660 nm, 60 seconds-16.6 minutes and 100-150 mW/cm2 respectively. Aminolevulinic acid, chlorine-e6, meta-tetrahydroxyphenylchlorin and photofrin were used as photosensitizer. The frequency of PDT application ranged between once and 12 times. Complete, partial and no response to PDT was shown by 27% to 100%, 5% to 50% and 0% to 25% of pre-malignant lesions, respectively. The recurrence rate of pre-malignant lesions was up to 36%.Conclusion: PDT is effective in the overall management of oral premalignant lesions.