Radiotherapy and concurrent chemotherapy (CRT) is superior to radiotherapy alone for the treatment of locally advanced, nonmetastatic squamous carcinoma of the head and neck (HNC). Three issues affect the use of CRT as primary treatment for advanced HNC. The first issue is the definition of advanced stage and the initial therapeutic choice of surgery or CRT and the role of post-CRT neck dissection. Function preservation considerations should guide the choice between surgery and CRT for patients with resectable disease. Fluorodeoxyglucose-positron emission tomography scanning may identify patients who require adjuvant neck dissection. The second issue is optimization of radiotherapy and chemotherapy schedules. Ideally, concurrent chemotherapy should be incorporated into radiotherapy (RT) regimens that would constitute optimal therapy were RT to be administered as single-modality treatment. Modified fractionation schemes constitute optimal single-modality RT. Platinum schedules other than bolus dosing every 3 to 4 weeks are effective and may be less toxic. The third issue is integration of biologically targeted therapy into CRT treatment programs. Epidermal growth factor receptor blockade enhances the effectiveness of RT alone. Its role and that of angiogenic blockade in CRT are under investigation.