Abstract: In the era of precision medicine, patients with lung cancer receive molecular subtype-based personalized management. The unmet clinical need initiated the concept of adaptive therapy, a novel personalized treatment strategy referring to the biomarker-directed treatment escalation or de-escalation based on the standard of care, aiming to improve efficacy, quality of life, and cost efficiency. Biomarkers are validated under specific clinical scenarios to dynamically and stably predict disease-free status or efficacy. The optimal clinical scenarios for adaptive therapy comprises post-treatment and radiologically lesion-free or metabolically inactive disease status. Several promising clinical situations are exploring de-escalation therapy, including epidermal growth factor receptor (EGFR)-mutated, totally resected non-small cell lung cancer (NSCLC), driver gene-negative, totally resected NSCLC, driver gene-negative, radiochemotherapy-treated, locally advanced NSCLC, and drug holidays for metastatic NSCLC. Therefore, circulating tumor DNA-minimal residual disease, (ctDNA-MRD) is considered an important biomarker. Concerning escalation therapy, this field is less well-supported with results, demanding further exploration. Related to future perspectives, more effort should be invested in focusing on patients with unmet clinical needs, even those with a standard of care, and providing biomarker-based adaptive therapy for efficacy and efficiency improvement.