The functional versatility of Wnt/β-catenin signaling can be seen by its ability to act in stem cells of the embryo and of the adult as well as in cancer stem cells. During embryogenesis, stem cells demonstrate a requirement for β-catenin in mediating the response to Wnt signaling for their maintenance and transition from a pluripotent state. In adult stem cells, Wnt signaling functions at various hierarchical levels to contribute to specification of different tissues. This has raised the possibility that the tightly regulated self-renewal mediated by Wnt signaling in stem and progenitor cells is subverted in cancer cells to allow malignant progression. Intensive work is currently being performed to resolve how intrinsic and extrinsic factors that regulate Wnt/β-catenin signaling coordinate the stem and cancer stem cell states.