It is well known that growth factors play an important role in normal cell proliferation by means of stimulation of growth factor receptors located on the surface of cells. Tumor cells express high levels of growth factor receptors that can theoretically serve as therapeutic targets in cancer treatment. Tyrosine kinase (type 1) growth factor receptors include the family of erbB receptors. The most extensively studied receptor in the erbB family is the human epidermal growth factor receptor (EGFR), also known as erbB1. Studies have shown that overexpression of EGFR is involved in the development and progression of head and neck squamous cell carcinoma (HNSCC). Blocking this receptor in HNSCC cell lines and animal models inhibits tumor growth. Strategies have been developed to target EGFR, including monoclonal antibodies, tyrosine kinase–specific inhibitors, ligand‐linked immunotoxins, and antisense approaches. Laboratory studies and clinical trials are under way to explore the safety and efficacy of these various approaches in a variety of cancers, including HNSCC. Preliminary results from early phase clinical trials are encouraging and may lead to the incorporation of these EGFR targeting strategies into the management of HNSCC. © 2002 Wiley Periodicals, Inc. Head Neck 25: 000–000, 2003