Head and neck cancer is the eighth most common cause of cancer death worldwide. Its incidence varies widely among different regions. In North America and the European Union, head and neck cancer accounts for 3% to 4% of all cancer diagnoses. Conversely, in Southeast Asia and Africa, head and neck cancer accounts for approximately 8% to 10% of all cancers1. Although the incidence of head and neck cancers has decreased slightly from 1975 to 2002 in the United States5, approximately 46 000 new cases are still expected in 2007 alone. Even if surgery and radiotherapy have remained the core therapy in squamous cell carcinoma of the head and neck (HNSCC). Radiotherapy following surgery was the standard approach to the treatment of locoregionally advanced (LA-HNSCC) resectable disease. However, some recent developments highlighted the expanding role of chemotherapy, which is increasingly being incorporated in the management of HNSCC. Concurrent chemo-radiotherapy has shown benefits in randomized trials; in addition, chemotherapy is used by itself as palliative therapy for patients with metastatic disease. As our understanding of the molecular and cellular mechanisms involved in cancer development improves, we are better able to identify potential targets for biological therapy and to apply novel strategies to the preclinical study and clinical treatment of head and neck cancers. Current avenues of research, focusing on clinical studies evaluating antibody directed therapies and gene replacement strategies for head and neck cancer are discussed