Although major progress has been made in surgery, radiation, and chemotherapy for the treatment of malignancy during the last 20 years, there has been little improvement in the survival of patients with recurrent or advanced head and neck cancer. Because of the ease and accessibility for surgery and their loco-regional biological behavior, head and neck cancers serve as an ideal model to test combined laser energy delivered via interstitial fiberoptics and chemotherapeutic agents activated by photo-thermal energy as an alternative, less invasive treatment for cancer. A number of investigators have shown that anthracyclines and cisplatin are likely candidates for light or heat activation in cancer cells. Maximum tolerated dose followed by photochemical and thermal activation via laser fiberoptics can improve treatment by sensitizing tumor response. The higher intratumor drug levels compared to systemic drug administration along with laser activation should also reduce systemic toxicity. In this article the authors analyze the concept of combining anti-cancer drugs and laser therapy and review the clinical application. In summary, the literature available suggests photochemotherapy with currently approved drugs and lasers may soon become an attractive alternative for cancer treatment.