Optimal treatment of acute myeloid leukemia (AML) in older adults (age ≥60 years) remains largely undefined, in part because of the inadequate response to available therapies, the poor prognosis relative to younger adults, the heterogeneity of the population, and the difficulty in determining who is fit for intensive therapy. In contrast to younger patients, there remains uncertainty about disease biology and molecular prognostic factors in elderly AML. While almost all patients may benefit from treatment, with the exception of reduced intensity allogeneic transplantation, there is little evidence that further intensifying therapy will improve outcomes. In fact, recent studies suggest that de-intensified treatment may in fact be superior and allow access to therapy for more patients. Both the disease and the patient must be approached holistically in order to make the best frontline treatment choice together. It is critical that we support well-designed clinical trials to develop more effective frontline therapies, develop more informative biomarkers, and to better understand who is a candidate for curative treatment.