The treatment of acute myeloid leukemia is evolving, with increased understanding of molecular pathogenesis allowing better risk stratification and development of new therapies. Tests to identify and drugs to target specific molecular abnormalities are improving remission rates and prolonging survival in patients with high-risk disease. Allogeneic hematopoietic stem cell transplantation remains an important curative therapy, with advances in donor availability and approaches to reduce transplant-related mortality making it applicable in many more patients. Considerations in identifying appropriate patients for targeted therapy and transplantation are presented.