The dialogue between Venugopal, MD, and Nabhan, MD, delves into unresolved challenges in treating chronic myeloid leukemia (CML). Venugopal emphasizes the need for targeted therapies in CML blast phase, distinguishing it from de novo AML or ALL. Despite advancements, current treatments fail to achieve optimal outcomes in these complex cases. Nabhan adds insights on first-line chronic phase treatment, highlighting the complexities of TKI selection due to availability, insurance hurdles, and cost. Imatinib, often preferred for its affordability, contrasts with higher-priced second-generation alternatives. The conversation underscores strides made in CML management but calls for further innovations and equitable access to therapies.