Photodynamic therapy (PDT) involves the use of a phototoxic drug which is activated by low powered laser light to destroy neoplastic cells. Multiple photosensitizers have been studied and tumors have been treated in a variety of head and neck sites over the last 30 years. PDT can effectively treat head and neck tumors, particularly those of the superficial spreading type, and the classic application of this technology has been in the patient with a wide field of dysplastic change and superficial carcinomatosis. Interstitial treatment has been used to treat more invasive cancer. Data is available from case series and institutional experiences, but very little randomized data is available. We review the mechanisms of action, historical development, available data, and current knowledge regarding PDT for the various head and neck subsites, and discuss possible future directions, with an emphasis on clinical application.