The FDA has approved pembrolizumab, an immune checkpoint inhibitor, for resectable locally advanced head and neck squamous cell carcinoma expressing PD-L1, following the pivotal phase 3 KEYNOTE-689 trial. Patients receiving pembrolizumab perioperatively showed longer event-free survival and significant tumor shrinkage pre-surgery. This marks the first checkpoint inhibitor approved in the curative perioperative setting, changing treatment protocols. The trial was led by Dana-Farber Brigham Cancer Center and Washington University investigators. This development offers a new therapeutic avenue for surgical management of head and neck cancer.