Acute myeloid leukemia (AML) is the most common acute leukemia in adults, with over 20,000 cases annually in the U.S. It arises from chromosomal abnormalities and mutations in genes involved in hematopoiesis, leading to the accumulation of poorly differentiated myeloid cells. AML is highly heterogeneous, with prognosis varying based on cytogenetic profiles. Recurrent mutations like FLT3-ITD, NPM1, and CEBPA help refine prognosis and guide treatment. Despite advances in supportive care, treatment remains based on cytarabine and anthracycline regimens, with allogeneic stem cell transplantation for eligible patients. Elderly patients often have poor outcomes due to intolerance of these regimens. Recent advances in AML treatment include the identification of genetic mutations, improved risk stratification, and novel therapies. The WHO classification system categorizes AML into six major entities based on genetic and clinical features. Prognostic factors include age, performance status, and cytogenetic changes. Cytogenetic abnormalities such as t(8;21), t(15;17), and inv(16) are associated with favorable outcomes, while complex karyotypes and mutations like FLT3-ITD and TP53 are linked to poor prognosis. Established treatments include induction therapy with the '7+3' regimen, followed by consolidation therapy. For elderly patients, hypomethylating agents like decitabine and azacitidine are used. Novel agents such as FLT3-ITD inhibitors (sorafenib, midostaurin, quizartinib, crenolanib) and STAT3 inhibitors show promise in improving outcomes. IDH1/IDH2 inhibitors are also being investigated. Clofarabine, a purine nucleoside analog, is effective in relapsed/refractory AML and is well-tolerated in elderly patients. Monoclonal antibodies like gemtuzumab ozogamicin (GO) and AGS67E target CD33 and CD37, respectively, showing potential in AML. Chimeric antigen receptor (CART) therapy is being explored for targeting AML cells while sparing healthy myeloid cells. Despite these advances, AML remains challenging, with poor long-term survival, especially in elderly patients. Novel targeted therapies and improved genetic profiling are expected to enhance treatment outcomes. Clofarabine and other oral agents offer promising options for elderly patients. The future of AML treatment lies in personalized, targeted approaches to improve survival and quality of life.Acute myeloid leukemia (AML) is the most common acute leukemia in adults, with over 20,000 cases annually in the U.S. It arises from chromosomal abnormalities and mutations in genes involved in hematopoiesis, leading to the accumulation of poorly differentiated myeloid cells. AML is highly heterogeneous, with prognosis varying based on cytogenetic profiles. Recurrent mutations like FLT3-ITD, NPM1, and CEBPA help refine prognosis and guide treatment. Despite advances in supportive care, treatment remains based on cytarabine and anthracycline regimens, with allogeneic stem cell transplantation for eligible patients. Elderly patients often have poor outcomes due to intolerance of these regimens. Recent advances in AML treatment include the identification of genetic mutations, improved risk stratification, and novel therapies. The WHO classification system categorizes AML into six major entities based on genetic and clinical features. Prognostic factors include age, performance status, and cytogenetic changes. Cytogenetic abnormalities such as t(8;21), t(15;17), and inv(16) are associated with favorable outcomes, while complex karyotypes and mutations like FLT3-ITD and TP53 are linked to poor prognosis. Established treatments include induction therapy with the '7+3' regimen, followed by consolidation therapy. For elderly patients, hypomethylating agents like decitabine and azacitidine are used. Novel agents such as FLT3-ITD inhibitors (sorafenib, midostaurin, quizartinib, crenolanib) and STAT3 inhibitors show promise in improving outcomes. IDH1/IDH2 inhibitors are also being investigated. Clofarabine, a purine nucleoside analog, is effective in relapsed/refractory AML and is well-tolerated in elderly patients. Monoclonal antibodies like gemtuzumab ozogamicin (GO) and AGS67E target CD33 and CD37, respectively, showing potential in AML. Chimeric antigen receptor (CART) therapy is being explored for targeting AML cells while sparing healthy myeloid cells. Despite these advances, AML remains challenging, with poor long-term survival, especially in elderly patients. Novel targeted therapies and improved genetic profiling are expected to enhance treatment outcomes. Clofarabine and other oral agents offer promising options for elderly patients. The future of AML treatment lies in personalized, targeted approaches to improve survival and quality of life.