Based on improved survival, PD-1 immune checkpoint inhibitors (± chemotherapy) have become the standard of care for patients with recurrent/metastatic SCCHN. However, in patients with locally advanced disease, the results of several clinical trials evaluating the addition of PD-(L)1 inhibitors to conventional chemoradiotherapy have been disappointing. Dr. Ezra Cohen, Dr. Yungan Tao, and Dr. Jonathan Schoenfeld discuss the potential reasons for immunotherapy failure, promising neoadjuvant immunotherapy approaches, and some ongoing, eagerly awaited trials that will hopefully help to define the role of immunotherapy in LA SCCHN.