Acute myeloid leukemia (AML) in older adults is a biologically and clinically distinct entity. Based on analysis of cytogenetic and molecular data, it is known that leukemic cells in older patients are intrinsically resistant to standard chemotherapy. Due to comorbid disease and impaired bone marrow stem cell reserve, older adults tolerate myelosuppressive chemotherapy poorly, with a treatment-related mortality rate of 25 percent. About 35 percent of adults under age 40 are cured, but the complete remission rate (likelihood of temporary disease eradication) is 45 percent in those over age 60, considerably lower than the 75% rate among younger patients, and the possibility of long-term disease free survival is 20 percent in those achieving remission or less than 10 percent overall. Standard allogeneic bone marrow transplantation is too dangerous to be considered as a means to eradicate minimal residual disease after remission is obtained and myelointensive chemotherapy is not a beneficial post-remission strategy in this age cohort. These disappointing results call for more effective and less toxic therapeutic options. Advances in our understanding of the pathophysiology of AML and promising early clinical data suggest that the era of truly targeted therapy in this difficult disease may soon be a reality.