Circulating tumor DNA (ctDNA) shed from cancer cells into the peripheral blood can be non-invasively collected and tested for the presence of tumor-specific mutations. Mutations identified in ctDNA can predict responses to targeted therapies and emerging evidence suggests that changes in ctDNA levels over time can be used to monitor response to therapy and detect disease recurrence. Given the emergence of targeted therapies in advanced non-small cell lung cancer (NSCLC), liquid biopsies utilizing ctDNA testing represent a powerful approach to genotype tumors and monitor for the development of resistance. Here, we review current and potential future clinical applications of ctDNA testing for patients with advanced NSCLC.