Advances in DNA sequencing methods have significantly expanded the potential clinical applications of analyzing circulating tumor DNA (ctDNA). This genetic information can identify the presence of targetable mutations and has been explored for cancer screening purposes. ctDNA can be obtained without the risks inherent to biopsy, allowing for serial assessments over time. Several studies have additionally suggested that ctDNA can be used to detect the presence of minimal residual disease (MRD) after surgical resection in several cancer types, including lung cancer. The ability to detect MRD would allow clinicians to tailor adjuvant therapies, which carry risks of significant toxicities and may benefit only select groups of patients. Here, we review the current state of ctDNA profiling methods and evaluate the evidence supporting the use of ctDNA analysis to assess for MRD. We discuss how MRD detection could help identify patients at increased risk of disease recurrence and thus guide treatment decisions for resectable lung cancer. Finally, we propose future steps to validate such approaches and expand the utility of these rapidly progressing technologies.