Advanced locoregional disease is the most frequent clinical situation in Head and Neck cancer. The standard of care for most clinicians is a multidisciplinary treatment with concomitant chemotherapy plus radiotherapy (CRT). However, retrospective studies have shown that in patients treated with CRT there was a relative increase in systemic relapse due to a lack of systemic control. For this reason a renewed interest has appeared for the incorporation of induction chemotherapy in the treatment of locally advanced Head and Neck Cancer. Furthermore new combination regimens with taxanes have shown to be more active than the classical cisplatin and 5-fluorouracil induction regimen. For these reasons ongoing trials are comparing induction chemotherapy followed by chemoradiotherapy with chemoradiotherapy alone. In this review, we will discuss the currently available data that support the design of these clinical trials as well as the future role of new agents in this clinical situation.