This review aims to identify and describe novel genetic and protein targets and their associated therapeutics currently being used or studied in the treatment of acute myeloid leukemia (AML). Over the past 5-6 years, several targeted therapies have been approved by the FDA for both newly diagnosed and relapsed/refractory AML, improving patient outcomes. Despite these advancements, outcomes remain poor for elderly patients and those with relapsed/refractory disease. The identification of molecular and genetic drivers and the development of therapeutics targeting these mechanisms have significantly improved patient outcomes. Key targets include BCL-2, FLT-3, IDH1/2, Menin, CD123, and CD47. BCL-2 inhibitors like Venetoclax have shown significant activity in AML, particularly in combination with other agents. FLT-3 inhibitors, such as Gilteritinib and Quizartinib, have been approved for both frontline and relapsed/refractory AML, improving response rates and survival. IDH1/2 inhibitors, including Enasidenib and Ivosidenib, have also demonstrated efficacy, especially in combination with other therapies. Menin inhibitors are showing promise in clinical trials, particularly in combination with other treatments. CD123 targeting therapies, such as Pivekimab and Tagraxofusp, are emerging as potential options. CD47 targeting antibodies, like Magrolimab, have shown encouraging results in phase 1 trials. While these treatments offer hope, they are effective for specific subsets of AML, and many patients still lack targeted therapies. Further research is needed to optimize the use of these novel therapeutics and to develop new targets for all patients with AML.This review aims to identify and describe novel genetic and protein targets and their associated therapeutics currently being used or studied in the treatment of acute myeloid leukemia (AML). Over the past 5-6 years, several targeted therapies have been approved by the FDA for both newly diagnosed and relapsed/refractory AML, improving patient outcomes. Despite these advancements, outcomes remain poor for elderly patients and those with relapsed/refractory disease. The identification of molecular and genetic drivers and the development of therapeutics targeting these mechanisms have significantly improved patient outcomes. Key targets include BCL-2, FLT-3, IDH1/2, Menin, CD123, and CD47. BCL-2 inhibitors like Venetoclax have shown significant activity in AML, particularly in combination with other agents. FLT-3 inhibitors, such as Gilteritinib and Quizartinib, have been approved for both frontline and relapsed/refractory AML, improving response rates and survival. IDH1/2 inhibitors, including Enasidenib and Ivosidenib, have also demonstrated efficacy, especially in combination with other therapies. Menin inhibitors are showing promise in clinical trials, particularly in combination with other treatments. CD123 targeting therapies, such as Pivekimab and Tagraxofusp, are emerging as potential options. CD47 targeting antibodies, like Magrolimab, have shown encouraging results in phase 1 trials. While these treatments offer hope, they are effective for specific subsets of AML, and many patients still lack targeted therapies. Further research is needed to optimize the use of these novel therapeutics and to develop new targets for all patients with AML.