Circulating tumor DNA (ctDNA) is increasingly used in the evaluation and management of EGFR-mutant non-small cell lung cancer (NSCLC). This review discusses the role of ctDNA in both early-stage and advanced NSCLC, highlighting its advantages over traditional tissue biopsies. ctDNA offers a non-invasive method for detecting genetic changes in tumors, which can guide treatment decisions and monitor disease progression. In early-stage NSCLC, ctDNA can help determine the need for adjuvant therapy and detect minimal residual disease (MRD) after surgery. In advanced NSCLC, ctDNA can identify resistance mechanisms to EGFR tyrosine kinase inhibitors (TKIs) and monitor treatment response. While tissue biopsies remain the gold standard, liquid biopsies using ctDNA are becoming a recommended alternative. Ongoing research aims to improve the sensitivity of ctDNA tests for early detection, refine treatment approaches based on ctDNA results, and explore other bodily fluids for better detection. Challenges include the limitations of current assays for disease recurrence detection and the need for standardized reporting. A systematic approach is crucial to ensure equitable access and integration of ctDNA into routine clinical practice. The review also discusses the potential of ctDNA in risk stratification, treatment escalation, and de-escalation strategies, emphasizing its role in improving patient outcomes and reducing adverse effects.Circulating tumor DNA (ctDNA) is increasingly used in the evaluation and management of EGFR-mutant non-small cell lung cancer (NSCLC). This review discusses the role of ctDNA in both early-stage and advanced NSCLC, highlighting its advantages over traditional tissue biopsies. ctDNA offers a non-invasive method for detecting genetic changes in tumors, which can guide treatment decisions and monitor disease progression. In early-stage NSCLC, ctDNA can help determine the need for adjuvant therapy and detect minimal residual disease (MRD) after surgery. In advanced NSCLC, ctDNA can identify resistance mechanisms to EGFR tyrosine kinase inhibitors (TKIs) and monitor treatment response. While tissue biopsies remain the gold standard, liquid biopsies using ctDNA are becoming a recommended alternative. Ongoing research aims to improve the sensitivity of ctDNA tests for early detection, refine treatment approaches based on ctDNA results, and explore other bodily fluids for better detection. Challenges include the limitations of current assays for disease recurrence detection and the need for standardized reporting. A systematic approach is crucial to ensure equitable access and integration of ctDNA into routine clinical practice. The review also discusses the potential of ctDNA in risk stratification, treatment escalation, and de-escalation strategies, emphasizing its role in improving patient outcomes and reducing adverse effects.