The present review aims at describing the role of MEIS1 during embryonic and adult hematopoiesis, its implication in leukemia, and at establishing how MEIS1 direct targeting might become a valuable tool for the treatment of MEIS1-expressing malignancies, in particular during MLL-rearranged (MLL-r) leukemia. This evidence concerns the gene MEIS1 and leukemia.