Targeted therapy is a very exciting era in the treatment of squamous cell carcinomas of the head and neck. After adding cetuximab to conventional chemotherapy and radiation therapy, we are strongly considering the role of induction chemotherapy with the addition of docetaxel. At the same time, other new treatments, especially targeted agents and novel combined regimens, are being evaluated in ongoing clinical trials. For example, several trials are attempting to combine docetaxel and cetuximab in chemoradiation or induction settings. However, in the near future we are likely to see a strong presence of targeted agents that have been found to be not only effective, but also less toxic than conventional chemotherapeutic agents. Their toxicity profiles make them eligible for addition to radiation treatment strategies, as well as other chemotherapy agents, or even for replacing these chemotherapy agents. In this article, we are going to review the indications and current role of cetuximab, tyrosine kinase inhibitors (gefitinib and erlotinib), dual inhibitors, IGF receptor inhibitors, as well as other agents that are in development for treatment of head and neck squamous cell carcinomas.