In the United States, the incidence of acute myeloid leukemia (AML) is approximately 3.5 cases per 100,000 persons per year. Approximately 13,000 people were diagnosed with AML in 2009 and 9,000 died of the disease, making AML the 6th leading cause of cancer death. Over the past three decades, AML survival has improved for younger patients with 5-year survival rates of greater than 60% for adults under the age of 45 years likely owing to improvements in induction and consolidation chemotherapy, allogeneic hematopoietic stem cell transplant (HSCT) and supportive care. Post-remission therapy with high-dose cytarabine-based regimens after cytarabine and anthracycline based induction has improved disease free and overall survival at the expense of increased treatment related mortality limiting its use in many older patients and those with significant comorbidities. Although allogeneic HSCT remains the standard of care for patients with poor risk AML or relapsed disease, advanced age, comorbidities and donor availability preclude this option for a large number of patients making improvement in the tolerability and efficacy of induction therapy an important goal.