We have entered the genomic sequencing era in the treatment of acute myeloid leukemia (AML); our patients increasingly and justifiably demand personalized treatment based on aberrations of their own leukemia. Except in rare cases we are not yet able to provide truly personalized therapy, so the question of "hope or hype?" posed by the American Society for Clinical Oncology (ASCO) for this educational topic is quite timely. The answer based solely on advances in genomic sequencing is "both". There is an element of expectation among the public that we are "almost there" in solving the genetic cancer puzzle, an expectation indeed based on hype. However, there is no question that ultimate success lies in understanding the genetic underpinnings of disease. When decades of research in molecular biology and immunology are combined with transformative advances in cancer genetics, the answer is undeniably that our patients finally have reason for hope. Here, we review selected novel therapies for AML in areas such as immunotherapeutics, epigenetics, kinase inhibition/pathway inhibition, and the marrow microenvironment.