Acute myeloid leukemia is a molecularly heterogenous disease caused by the rapid expansion and impaired differentiation of malignant myeloid progenitors. Overall, outcomes remain poor, and more than half of patients develop relapsed or refractory disease after front-line therapy. Allogeneic hematopoietic stem cell transplant (HCT) remains the best chance for cure for eligible patients, and the development of novel therapies including BCL2, FLT3, IDH1/2 and menin inhibitors, which are efficacious yet generally more tolerable, have enabled better bridging to prompt HCT. Despite the early success of targeted therapies, more generalized and efficacious therapeutic approaches remain in need, and numerous targeted immunotherapeutic agents (including CAR-T, bispecific and trispecific antibody therapies) are currently under investigation.