Leukemia and lymphomas are diverse group of diseases that arise from hematopoietic and immunologic cells. The global statistics of morbidity and mortality due to these multigenic disorders call for therapeutic interventions that not only aid in increased survival of the patients but also help in better disease management of terminally ill patients. Leukemia has four major sub types, of which, acute myeloid leukemia (AML) most commonly affect the middle aged and elderly population. Due to its heterogeneous nature and poor therapeutic outcome among adults, AML remains the focus of clinicians and scientist alike. Despite having well-established animal models for the study of leukemia, we still need to improvise and upgrade models that would befit the present knowledge of the disease and its genomics. Here we discuss the murine models used in development of novel and rational treatments for AML. We also discuss the future of animal models in translational cancer research. © 2019 Elsevier Inc. All rights reserved..