OBJECTIVES:  The objective of this study was to conduct a comprehensive assessment of economic burden associated with CML outlining the contributions of pertinent cost components to identify unmet needs and opportunities METHODS:  Systematic literature review was conducted in PubMed from 2006-2016 and conference proceedings of ASH, ASCO and ISPOR from 2013-2016. Search was limited to US-based human studies, published in English. Data on study and patient characteristics, and cost components were extracted from eligible studies. Cost components (converted to 2016$) included mean costs related to drugs, adverse event (AE), out-of-pocket (OOP), inpatient/outpatient, and office visits. Costs were reported by TKI-use, adherence levels and switching/failure as available. RESULTS:  Of 126 titles screened, 14 studies (13 database analyses, 1 survey) were included. Annual cost paid by insurance plan (plan paid) for TKI-users was $69,812 vs. $58,616 for non-TKI users, and OOP costs ranged from $3,084-$3,756. Among TKI-users, total annual plan paid and OOP costs were $92,823 for 1st-line dasatinib/nilotinib and $71,292 for 1st-line imatinib. Total annual cost of patients on imatinib and with high adherence was $52,552-$65,093 and with low adherence was $119,893-$163,387. Annual cost inpatient and outpatient for AEs was $17,927 for femoral arterial stenosis and $15,966 for peripheral arterial occlusive disease among TKI-users. The costs related to treatment switching and failure were also captured. Indirect costs, OOP costs for 2nd generation TKIs, cost of AE by TKI, and cost of adherence for TKIs other than imatinib was not available. CONCLUSIONS:  The economic burden in CML is significant and driven by prescription, inpatient and outpatient costs and influenced by adherence. Costs related to AEs, switching, and treatment failure add to that burden. Gaps need to be addressed to better understand the economic burden of CML and identify opportunities related to unmet needs. Generic imatinib may lead to potential cost-savings.