Present therapy of head and neck cancer patients includes surgical procedures, radiotherapy and sometimes chemotherapy. Over recent decades no dramatic improvements have been obtained with these treatment modalities with respect to efficacy and associated morbidity. Of patients with early stage disease (stage I and II), about 25% cannot be cured, while for patients with advanced disease (stage III and IV) this percentage may be as high as 70%. However, owing to advances in our knowledge of molecular biology, immunology, (bio)chemistry and biology of head and neck squamous cell carcinoma (HNSCC), new perspectives on therapy are arising. After several years of optimization several new therapeutic approaches are leaving their infancy and are being evaluated in clinical trials with HNSCC patients. Among other approaches, photodynamic therapy, gene therapy and antibody-based therapy are attracting most attention. The basic concepts and the potential applications of these treatment modalities in the management of head and neck cancer are discussed in this paper.