Cancer stem cells may be responsible for tumor initiation and maintenance. The molecular mechanisms that control cancer stem cells are related to alterations in various signaling pathways, including the Wnt/β-catenin signaling pathway. The canonical Wnt/β-catenin signaling pathway is one of the major signaling systems in stem and progenitor cells, and aberrant activation of the Wnt/β-catenin signaling pathway is common in human cancers. As with β-catenin, FoxM1 has been found to play important roles in a number of cancers. In this review, we discuss the evidence that FoxM1 affects the expression and function of a variety of genes that are critical to the survival, proliferation, invasion, angiogenesis, and self-renewal of cancer stem cells. We highlight the pivotal roles of the Wnt/β-catenin and FoxM1 signaling pathways in neural stem and progenitor cells and glioma stem cells. We also discuss the evidence for cross-talk between the β-catenin and FoxM1 signaling pathways in the regulation of the stemness and tumorigenicity of glioma stem cells. Cancer Res; 72(22); 5658–62. ©2012 AACR.