The treatment of acute myeloid leukemia has been associated with dismal outcomes despite available therapies. The morbidity and mortality associated with acute myeloid leukemia (AML) are most profound in older patients who account for the majority of cases. The 5-year survival of AML patients over age 65 years has remained 5% for decades. However, for the first time since the development of 7+3 induction chemotherapy in the 1970s, there is reason to believe that outcomes can and will improve. The understanding of the biology of AML has led to the development of targeted therapies that have shown great promise in this regard. Therapeutic interventions can lead to meaningful responses with improvement in hematopoietic function and much more acceptable toxicity profiles compared with intensive therapy. The therapeutic paradigms for older AML patients have shifted. Nevertheless, the diagnosis most often comes late in life, when patients are more likely to have impaired functional status and suffer from other comorbid illnesses. Therefore, the oncologist must be fully engaged with the patient, discussing goals of therapy and end-of-life issues, in a shared decision making process.