Simple Summary Acute myeloid leukemia is the most common type of acute leukemia in adults. It is associated with poor outcomes, especially in older patients. Treatments based exclusively on chemotherapy do not achieve high overall survival rates, or in any case, only in a small group of patients. The objective of this review is to discuss the treatment of acute myeloid leukemia from newly approved therapeutic drugs to newer strategies. In first line, the combination of new targeted therapies with standard chemotherapy achieves better outcomes in "fit" patients. For "unfit" patients the combination of different targeted therapies provides them with better overall survival rates, with limited toxicity. As for refractory and relapsed acute myeloid leukemia, development of immunotherapy or new targeted therapies brings new hope. Acute myeloid leukemia is a heterogeneous disease defined by a large spectrum of genetic aberrations that are potential therapeutic targets. New targeted therapies have changed the landscape for a disease with poor outcomes. They are more effective than standard chemotherapy with a good safety profile. For "fit patients" in first-line, the combination of gemtuzumab ozogamicin or midostaurin with intensive chemotherapy or Vyxeos is now considered the "standard of care" for selected patients. On the other hand, for "unfit patients", azacitidine-venetoclax has been consolidated as a frontline treatment, while other combinations with magrolimab or ivosidenib are in development. Nevertheless, global survival results, especially in relapsed or refractory patients, remain unfavorable. New immunotherapies or targeted therapies, such as Menin inhibitors or sabatolimab, represent an opportunity in this situation. Future directions will probably come from combinations of different targeted therapies ("triplets") and maintenance strategies guided by measurable residual disease.