The incidence of acute myeloid leukemia (AML) is increasing with age. As the results associated with standard intensive chemotherapy remain particularly disappointing in older patients, they represent an ideal target population for clinical and therapeutic investigations. Current attempts are to better define those who may draw a significant benefit from intensive chemotherapy, in order to test new less intensive approaches in the remaining patients. Hopefully, a lot of promising alternative therapies are emerging, including hypomethylating agents, histone deacetylase inhibitors, monoclonal antibodies, or chemotherapeutic agents such as cloretazine or clofarabine. Reduced-intensity conditioning stem cell transplantation or other various immunological approaches represent another way of investigation.