Nasopharyngeal carcinoma (NPC), an endemic tumor in southern China, has three unique etiologic factors, including genetic susceptibility, chemical carcinogens, and association with Epstein-Barr virus (EBV) infection. Recent identification of critical genetic changes in this cancer has allowed the description of a multistep model for the pathogenesis of NPC. NPC is highly radiosensitive and chemosensitive. Attempts have been made to improve treatment results by integrating radiotherapy with some form of chemotherapy. Here, we review the current evidence available on the various chemotherapy-radiotherapy sequencing approaches and seek to define the optimal integration of radiotherapy and chemotherapy. Despite consistently high response rates to platinum-based neoadjuvant chemotherapy, none of six randomized studies of neoadjuvant and/or adjuvant chemotherapy showed any improvement in overall survival, although two did demonstrate significant improvement in local control rates and progression-free survival. However, three randomized studies of concurrent cisplatin-radiotherapy one with, and two without, adjuvant chemotherapy demonstrated significant improvement in progression-free survival and two of these have demonstrated improvement in overall survival. Preliminary data on the use of neoadjuvant chemotherapy followed by concurrent chemoradiation have been highly encouraging. Concurrent cisplatin-radiation with or without adjuvant chemotherapy should be considered as standard practice for locoregionally advanced NPC. The addition of neoadjuvant chemotherapy warrants further investigation and appears to be the most likely approach to further improve treatment results.