Maria Arcila, MD, Memorial Sloan Kettering Cancer Center, New York, NY, considers some of the major challenges facing the uptake of cell-free DNA (cfDNA) analysis in the clinic for patients with lung cancer. The current lack of international guidelines for the extraction and assessment of cfDNA remains a key challenge that needs to be addressed. Another important consideration is that not all patients shed sufficient levels of DNA into the circulation for detection, meaning negative results must be interpreted with caution to avoid underdiagnosis. This interview took place at the World Conference on Lung Cancer (WCLC) 2021.