Imatinib mesylate (imatinib) is now a standard treatment for patients with chronic myeloid leukemia (CML). Although imatinib is known to have a potential impact on various infectious organisms by altering the T-cell mediated immune response, only two cases of hepatitis B virus (HBV) reactivation during imatinib treatment have actually been reported. The role of liver transplantation (LT) after fatal HBV reactivation in patients with potentially treatable or curable hematologic malignancy is also unknown. Therefore, this report presents a case of fatal HBV reactivation during imatinib treatment for CML, where the patient is rescued by LT. Following a successful living donor LT, the liver function improves rapidly and the patient remains in complete cytogenetic remission after retreatment with imatinib for 6 months. The present report also covers the role of tyrosine kinase inhibitor in triggering HBV reactivation and a literature review of fulminant hepatic failure in CML patients taking imatinib.