Locally advanced SCCHN (LA-SCCHN) is generally treated by a combination of chemotherapy, irradiation and/or surgery. Timing of the chemotherapy has for long been a matter of debate but concurrent chemoradiation was widely adopted as standard of care for locally advanced squamous cell carcinoma of the head and neck after the publication of a large meta-analysis which demonstrated that concurrent chemoradiation confers an absolute survival benefit of 8% at 2 and 5 years. Induction chemotherapy has some appealing advantages including the opportunity of assessing tumor response and selecting the patients who are candidates for organ preservation. The cisplatin-fluorouracil combination has been the induction regimen of choice for two decades but has recently been superseded by a combination of cisplatin, fluorouracil and a taxane which can be considered the standard regimen when induction chemotherapy is appropriate. Multiple large randomized trials designed to compare sequential induction, i.e., chemotherapy followed by CRT to CRT alone are currently underway. New challenges are the integration of targeted therapies into the current treatment strategies and the identification of prognostic biomarkers and of factors predicting the response to treatment which would help to select patients who are likely to benefit most from induction chemotherapy.