Several different approaches have been tested in an effort to integrate chemotherapy into definitive non-operative management of squamous cell head and neck cancer. In phase III randomized trials and in meta-analyses, the concomitant use of chemotherapy and radiation has proven to be the most consistently successful, and to produce both locoregional control and survival benefits, when compared to radiation therapy alone. Large, multi-institutional and cooperative group studies have now established high-dose single-agent cisplatin and concurrent radiation therapy as the standard of care for patients with advanced nasopharynx cancer, for patients with unresectable head and neck tumors, and as a postoperative adjuvant for patients with high-risk pathologic features. This same treatment regimen also has been demonstrated to be the most effective multi-modality treatment strategy for larynx preservation. Future investigation will focus on optimizing the concomitant chemotherapy and radiotherapy schedules used, integrating targeted agents into these established treatment schedules, addressing the problem of distant metastases, minimizing both acute and late toxicities, and identifying the most appropriate patient populations for this kind of aggressive treatment.