More than half of patients with head and neck cancer present with locally advanced disease, and high-risk patients continue to have a poor prognosis. The treatment of locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) is complex and requires a multidisciplinary team approach. Dr. Jonathan Schoenfeld, Dr. Ezra Cohen, and Dr. Yungan Tao discuss the current treatment strategies for these patients and challenges in achieving cure while preserving function and quality of life.