Over 1,500 patients have been treated with PDT using Photofrin, HPD, ALA, or Foscan for head and neck cancers. These patients include a mixture of presentations including primary, recurrent, and metastatic lesions. The predominant histology is squamous cell carcinoma, but other histologies treated include mucosal melanoma, Kaposi’s sarcoma, adenocarcinoma, metastatic breast carcinoma, and adenoid cystic carcinoma. Several multi-institutional phase II clinical trials evaluating PDT treatment of head and neck cancers have demonstrated the efficacy of this minimally invasive therapy in the treatment of early oropharyngeal primary and recurrent cancers as well as the palliative treatment of refractory head and neck cancers. Patients with early stage cancers or early recurrences in the oral cavity and larynx (Cis, T1, T2) tend to have an excellent response to PDT. Of 518 patients treated with Cis, T1, or T2 cancers of the oral cavity, larynx, pharynx, and nasopharynx, 462 (89.1%) obtained a complete clinical response after one PDT treatment. Laryngeal cancers, comprising 171 patients in this group, obtained a durable complete response rate of 89% with up to a 16-year follow-up. Photodynamic therapy is as effective as conventional therapies for the treatment of early (Cis, T1, T2) squamous cell cancers of the head and neck. It is also a promising therapy to be used in association with surgery to increase tumor-free margins and therefore increase cure rates.