With the exception of the minority of patients with acute myelocytic leukemia who are considered potentially cured by chemotherapy, hematopoietic cell transplantation (HCT) has traditionally been the recommended approach for those patients achieving complete remission who meet the criteria for HCT and have an appropriate stem-cell donor. This decision has become more complex with the discovery of new risk factors, such as genomic abnormalities and minimal residual disease, especially in younger populations. Patients younger than age 60 years who are considered fit and who do not harbor poor prognostic features are felt still to have a high likelihood of cure without having to undergo HCT. Here, we discuss the role that these emerging risk factors play in the decision to undergo transplantation, but emphasize that this remains a decision made jointly by the patient, the treating hematologist, and the transplant physician.