Growth factor receptors play a crucial role in the cell proliferation pathways involved in the development of cancer. One such receptor, the epidermal growth factor receptor (EGFR), is upregulated in many types of human tumors, particularly head and neck squamous cell carcinoma (HNSCC). EGFR overexpression in HNSCC has been the basis for investigation of therapeutic strategies that target EGFR. EGFR-blocking methods under evaluation involve immunotoxins, monoclonal antibodies, EGFR-specific tyrosine kinase inhibitors, and antisense approaches. These molecular targeting tactics have produced a number of agents that are currently in various stages of preclinical investigation, along with clinical trials to assess their potential as anticancer treatments.