The treatment of patients with locoregionally advanced or unresectable squamous cell carcinoma of the head and neck is complex and associated with significant toxicities. During the past 30 years, there has been an ongoing shift in what is perceived as the best treatment approach. Differing radiation techniques have been employed, and chemotherapy has been incorporated in both sequential and concomitant strategies. In this article, we will review the available data regarding many of the advances that have been achieved. We will also discuss the most relevant recent clinical trials, as well as ongoing trials that will hopefully answer some of the questions that remain as we attempt to best treat this patient population