The word Leukemia was coined nearly 200 years ago by Rudolf Virchow. Once a death sentence, Acute Myeloid Leukemia (AML) is now a treatable condition. The introduction of “7 + 3” chemotherapy, originally reported from the Roswell Park Memorial institute in Buffalo, New York, in 1973, changed the treatment paradigm for AML. About twenty-seven years later, FDA approved the first targeted agent, gemtuzumab, to be added to this backbone. During the last seven years, we have had ten new drugs approved for the management of patients with AML. Work by many dedicated scientists led to AML achieving the elite status of being the first cancer to have the whole genome sequenced using next-generation sequencing. In the year 2022, we witnessed the introduction of new classification systems for AML by the international consensus classification and the world health organization, both emphasizing molecular classification of the disease. In addition, the introduction of agents such as venetoclax and targeted therapies have changed the treatment paradigm in older patients ineligible for intensive therapy. In this review, we cover the rationale and evidence behind these regimens and provide insights into the newer agents.