Simple SummaryIn hematological malignancies, specifically in acute myeloid leukemia, aberrant stem cells, also known as leukemic stem cells, may be responsible for the relapse of the disease. Since several authors have related the quiescence and chemoresistance of leukemic stem cells with the Wnt/β-catenin signaling pathway, new approaches to chemosensitize this population should be studied. Therefore, in this review, we summarize the current information about the Wnt/β-catenin signaling pathway in hematology.AbstractWnt signaling is a highly conserved pathway in evolution which controls important processes such as cell proliferation, differentiation and migration, both in the embryo and in the adult. Dysregulation of this pathway can favor the development of different types of cancer, such as acute myeloid leukemia and other hematological malignancies. Overactivation of this pathway may promote the transformation of pre-leukemic stem cells into acute myeloid leukemia stem cells, as well as the maintenance of their quiescent state, which confers them with self-renewal and chemoresistance capacity, favoring relapse of the disease. Although this pathway participates in the regulation of normal hematopoiesis, its requirements seem to be greater in the leukemic stem cell population. In this review, we explore the possible therapeutic targeting of Wnt to eradicate the LSCs of AML.