New research and clinical interest are converging on menin inhibitors as a targeted strategy for KMT2A-rearranged acute leukemias. Studies show menin blockade disrupts the leukemogenic program driven by KMT2A fusions, yielding deep antiproliferative effects in models and early clinical responses in heavily pretreated patients. The evidence positions menin inhibitors as a mechanistic precision therapy option for a genomically defined subset of AML and ALL. Menin is a chromatin-interacting cofactor required for KMT2A fusion–mediated transcription. The emerging data provide rationale for combination trials with epigenetic agents and immunotherapies, and underscore near-term opportunities to move menin inhibitors into front-line and pediatric studies where KMT2A rearrangements carry high risk.