Abstract: Although the advent of tyrosine kinase inhibitor (TKI) has changed treatment prospects for patients with chronic myeloid leukemia (CML), long-term medication use may lead to adverse events, including drug-related toxicity, increased economic burden, and decreased quality of life. Treatment-free remission (TFR) refers to the state in which CML patients maintain deep molecular remission (DMR) without clinical or hematological recurrence after the discontinuing TKI therapy. Over the past two decades, TFR has become a new goal of CML treatment and has been incorporated into recommendations in authoritative guidelines, including the European Leukemia Network (ELN) and the National Comprehensive Cancer Network (NCCN) in the United States. This review discusses TFR evolution and predictive factors, CML recurrence mechanisms and coping strategies, secondary treatment discontinuation, safety and future TFR concept development directions. These insights aim to assist clinicians in accurately assessing the feasibility and suitability of TFR for patients and exploring future optimization strategies.