Recently, a number of targeted therapies using either monoclonal antibodies or tyrosine kinase inhibitors directed against the epidermal growth factor receptor (EGF-R), the vascular endothelial growth factor (VEGF) and its receptor (VEGF-R), the phosphatidyl-inositol-3-kinase (PI3K) and the mammalian target of rapamycin (mTOR) has been approved for the treatment of HNSCC, such as cetuximab, panitumumab, zalutumumab, gefitinib, erlotinib, lenvatinib, lapatinib, bevacizumab, sorafenib, rapamycin and everolimus, with significant, but still limited response rates ranging between 10–15%. Here, EGFR is linked to head and neck squamous cell carcinoma.