With a few subgroups as exceptions, such as younger patients with more favorable genetic disease, improvement in the treatment of acute myeloid leukemia has been slow. There is a possibility that improving the quality of remission can reduce the risk of relapse. Escalation of daunorubicin dose, addition of Ab-directed chemotherapy, and alternative nucleoside analogs in induction may displace the longstanding standard of "3 + 7" daunorubicin + cytarabine (Ara-C) as induction, and several prognostic factors are emerging that enable a more personalized approach to postinduction treatment, in particular, which patients should be offered allogeneic transplantation in first remission. In addition to providing prognostic information, molecular characterization provides potential therapeutic targets and, in some cases, an opportunity to more precisely monitor residual disease. With few exceptions, the predictive value of prognostic factors (ie, what therapy to adopt) has yet to be established. A major challenge is the treatment of older patients with acute myeloid leukemia (AML), who represent the majority of patients with this disease. Only about half of older AML patients will enter complete remission (CR) with conventional chemotherapy and, of these, most will relapse within 2 years. Little impact has been made on these dismal outcomes over the past 3 decades, and new treatments and approaches to trial design are required. Another population of concern is older AML patients who are not considered to be fit for an intensive approach based on concerns about their ability to withstand the consequences of treatment. This group is not easy to define objectively, but age represents a useful surrogate because it is associated with more chemoresistant disease and medical comorbidity. Older patients represent a therapeutic challenge, but several new treatments may offer some potential to improve their situation.