A clonal hematopoietic disease, acute myeloid leukemia (AML) is characterized by abnormal proliferation of early precursors of myeloid cells and blasts. It represents a heterogeneous disease group with a considerably complex biology and pathophysiology. Various translocations, chromosome copy number changes, and mutations have been described in AML, and a few of them help define the diagnosis, prognosis, and management. Cytarabine and anthracycline-based combination regimens followed by the allogeneic stem cell transplant remain the optimal treatment in most cases. However, older age and decreased tolerance to conventional therapies pose a major challenge for the conventional therapies, leading to the development of effective and less toxic therapy modalities as reviewed in this article.