In this episode of The AML Expert Series, Amer Zeidan, MBBS, Yale School of Medicine, New Haven, Connecticut, and Eunice S. Wang, MD, Roswell Park Comprehensive Cancer Center, Buffalo, New York, discuss the evolving landscape of treatment strategies for relapsed or refractory acute myeloid leukemia (AML). They emphasize the critical role of comprehensive mutational profiling at diagnosis and relapse, as outlined in the 2025 NCCN guidelines, to inform targeted therapies. The discussion highlights the integration of novel agents, such as IDH and FLT3 inhibitors, into treatment regimens, aiming to improve patient outcomes in relapsed or refractory AML