Circulating tumor DNA is a novel biomarker with emerging uses in the clinical care of patients with cancer, including non-small-cell lung cancer. Already approved for use in various clinical settings in patients with metastatic non-small-cell lung cancer, recent research has focused on the ability of circulating tumor DNA to predict relapse of patients with localized disease after treatment with curative intent. Identifying patients at increased risk of relapse after treatment with curative intent remains challenging, but several groups have identified circulating tumor DNA kinetics as a potential means of aiding our risk stratification. Herein, we discuss current research that identifies longitudinal circulating tumor DNA kinetics as a highly sensitive and specific marker for relapse. Then, we identify important clinical considerations and challenges for moving forward with further studying and eventually using this biomarker for patients with localized disease in clinic.