Susanne Flach, BM BCh, PhD, Ludwig-Maximilians-University, Munich, Germany, reflects on the use of circulating tumor DNA (ctDNA) approaches in head and neck squamous cell carcinoma, highlighting the importance of improving sensitivty, reducing cost of next-generation sequencing and standardization of techniques. This interview took place at the American Society of Clinical Oncology (ASCO) 2022 Annual Meeting in Chicago, IL.