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Background/Objectives: The introduction of tyrosine kinase inhibitors has transformed chronic myeloid leukemia into a chronic condition with near-normal life expectancy, shifting clinical priorities toward long-term tolerability, symptom burden, and health-related quality of life. This review aims to synthesize current evidence on patient-reported outcomes and quality of life in chronic myeloid leukemia, with particular focus on fatigue, differences across therapies, associations with molecular response and treatment-free remission, and health utility outcomes. Methods: A narrative review of published clinical trials, observational studies, and patient-reported outcome research in chronic myeloid leukemia during the tyrosine kinase inhibitor era was conducted. Evidence from generic, cancer-specific, and disease-specific quality-of-life instruments was examined, together with studies evaluating dose reduction, treatment discontinuation, and survivorship outcomes. Results: Across studies, patients with chronic myeloid leukemia experience persistent impairments in quality of life compared with the general population despite effective disease control. Fatigue consistently emerges as the dominant symptom associated with functional limitation and reduced well-being. Comparative analyses across tyrosine kinase inhibitors demonstrate generally modest and inconsistent differences in global quality of life. Deeper molecular responses, dose reduction, and treatment-free remission are commonly associated with stabilization or improvement in patient-reported outcomes, although symptoms may persist in a subset of patients. Methodological limitations include heterogeneity of instruments, predominance of cross-sectional designs, and lack of established minimal important differences for disease-specific measures. Conclusions: In the modern treatment era, chronic myeloid leukemia is characterized by excellent survival but an ongoing quality-of-life burden, largely driven by fatigue. Future research should prioritize longitudinal patient-reported outcome collection, methodological standardization, and development of clinically meaningful thresholds to better align disease control with patient-centered outcomes.