Acute myeloid leukemia (AML) has seen significant advancements in treatment over the past five to six years, with several FDA-approved targeted therapies improving outcomes for patients, particularly those with relapsed/refractory disease. These therapies target molecular mechanisms involved in AML pathogenesis, including BCL-2, FLT-3, IDH1/2, Menin, CD123, and CD47. Venetoclax, a BCL-2 inhibitor, has shown efficacy in combination with hypomethylating agents and low-dose cytarabine, improving survival and remission rates. FLT-3 inhibitors like Gilteritinib and Quizartinib have been approved for relapsed/refractory AML, with Gilteritinib also showing promise in the frontline setting. IDH1/2 inhibitors such as Enasidenib and Ivosidenib are effective in patients with IDH mutations, while Menin inhibitors are being tested in clinical trials for KMT2A-rearranged and NPM1-mutated AML. CD123-targeting therapies, including ADCs and CAR-T cells, are emerging as potential options, and CD47 inhibitors like Magrolimab are showing promise in improving phagocytosis of AML cells. Despite these advances, many patients, especially those with TP53 mutations, remain challenging to treat. Ongoing research aims to identify additional therapeutic targets and optimize existing treatments to improve long-term outcomes for AML patients.Acute myeloid leukemia (AML) has seen significant advancements in treatment over the past five to six years, with several FDA-approved targeted therapies improving outcomes for patients, particularly those with relapsed/refractory disease. These therapies target molecular mechanisms involved in AML pathogenesis, including BCL-2, FLT-3, IDH1/2, Menin, CD123, and CD47. Venetoclax, a BCL-2 inhibitor, has shown efficacy in combination with hypomethylating agents and low-dose cytarabine, improving survival and remission rates. FLT-3 inhibitors like Gilteritinib and Quizartinib have been approved for relapsed/refractory AML, with Gilteritinib also showing promise in the frontline setting. IDH1/2 inhibitors such as Enasidenib and Ivosidenib are effective in patients with IDH mutations, while Menin inhibitors are being tested in clinical trials for KMT2A-rearranged and NPM1-mutated AML. CD123-targeting therapies, including ADCs and CAR-T cells, are emerging as potential options, and CD47 inhibitors like Magrolimab are showing promise in improving phagocytosis of AML cells. Despite these advances, many patients, especially those with TP53 mutations, remain challenging to treat. Ongoing research aims to identify additional therapeutic targets and optimize existing treatments to improve long-term outcomes for AML patients.