This chapter discusses novel therapies in head and neck cancers, where epidermal growth factor (EGF), transforming growth factor (TGF)-α, amphiregulin, CRIPTO, $BT-cellulin, heparin-binding EGF (HB-EGF) and epiregulin are known ligands for epidermal growth factor receptor (EGFR). Gefitinib is a reversible EGFR-specific tyrosine kinase inhibitor, and has also been associated with a pulmonary toxicity of interstitial lung disease in approximately 1 percent of patients, one-third of which are fatal. Erlotinib is an oral, highly selective, reversible EGFR tyrosine kinase inhibitor, where tumor cells can persist and grow in situ without neovascularization until they reach the size of 2–3 mm. Cetuximab and gefitinib were combined in preclinical studies and were found to have a synergistic effect. Hepatocyte growth factor, also known as Scatter factor, is a cytokine linked with tumor progression and metastasis of cancer cells.