Recently, the integration of radiotherapy and chemotherapy has advanced the treatment of locally advanced squamous cell carcinoma of the head and neck (SCCHN), allowing functional organ preservation while improving locoregional control and overall survival compared with radiotherapy alone. However, as recurrences remain inevitable, there is an absolute need for alternative modes of therapeutic intervention. Moreover, the use of chemotherapy and radiotherapy also increases the incidence of toxicities such as mucositis, myelosuppression, xerostomia, and dysphasia. More recently, the use of molecular-targeted drugs, which minimally adds to the existing toxicities, along with cytotoxic drugs and radiotherapy has been intensively investigated. Cetuximab is a chimeric IgG1 monoclonal antibody that specifically blocks the epidermal growth factor receptor. In a randomized trial of radiotherapy with or without cetuximab for locally advanced SCCHN, the addition of cetuximab significantly improved the locoregional control and overall survival without an increase in adverse events. Furthermore, a randomized trial of 5-FU and cisplatin with or without cetuximab for recurrent/metastatic SCCHN demonstrated a significant survival benefit for cetuximab combination arms compared with 5-FU and cisplatin arms alone. Based on these findings, many molecular-targeted drugs have been investigated in the treatment of the head and neck cancer to ensure better clinical outcomes in the near future.