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Acute myeloid leukemia (AML) remains a biologically heterogeneous disease with historically limited targeted therapies and poor outcomes. The development of menin inhibitors represents a promising shift, particularly for patients harboring KMT2A rearrangements (KMT2Ar) and NPM1 mutations (NPM1m). This manuscript reviews the molecular rationale of menin inhibition for aberrant homeobox/myeloid ectopic insertion site 1 (HOX/MEIS1)-driven gene expression and leukemogenesis, clinical trial outcomes, and safety data for menin inhibitors, with a focus on recently FDA-approved revumenib and several other agents in development, ziftomenib (KO-539), bleximenib (JNJ-75276617), and icovamenib (BMF-219). We also focused our discussion on future directions to include resistance mechanisms, biomarker identification and monitoring strategies, and combination therapies. Menin inhibition is now being clinically integrated into relapsed/refractory and frontline treatment settings.