The mammalian epidermis is an excellent model with which to analyze the factors that regulate adult stem cell renewal, lineage selection, and tumor formation. One of the key regulators of all three processes is beta-catenin, the main cytoplasmic effector of the canonical Wnt signaling pathway. In this chapter, we review some of the ways in which beta-catenin exerts its effects on cultured human epidermal cells and in genetically modified mice. We highlight the importance of the timing and level of activation and discuss some of the pathways activated downstream from beta-catenin. Finally, we demonstrate the importance of Lef/Tcf-independent beta-catenin signaling through interaction with the vitamin D receptor.