Before the introduction of the BCR-ABL1 tyrosine kinase inhibitor (TKI) imatinib, chronic myeloid leukemia (CML) was the leading indication for allogeneic hematopoietic stem cell transplant (HSCT), and allogeneic HSCT remains the only treatment recognized as curative for CML. The success of imatinib and other TKIs (e.g., nilotinib, dasatinib) has made allogeneic HSCT a later-line therapy that is reserved only for advanced-phase, high-risk, or TKI-resistant patients with CML. Accumulating evidence from clinical trials investigating treatment-free remission suggests that TKIs may also provide an operational cure for some patients with CML. Herein, we discuss the concept of cure in CML and the current roles of both HSCT and TKIs in the treatment of CML.