In this video, Naval G. Daver, MD, a professor and director of the Leukemia Research Alliance Program, MD Anderson Cancer Center, Houston, Texas, and Uma Borate, MBBS, Acute Leukemia Clinical Section Head, The Ohio State University, Columbus, Ohio, discuss complex cases of relapsed or refractory FLT3-mutated AML, emphasizing the necessity of retesting for FLT3 mutations at relapse, as patients can lose the mutation after intensive chemotherapy. Drs Daver and Borate also reviewed the use of gilteritinib, an FDA-approved FLT3 inhibitor, as a treatment option for relapsed FLT3-mutated AML, with a preference for combination therapies to enhance response rates. Additionally, they highlighted the importance of supportive care, including prophylactic antibiotics, and the evolving landscape of oral therapies in AML treatment.