The article represents a literature review that summarizes current knowledge on the role of Wnt/catenin signaling, a highly conserved developmental pathway, in stem cells biology. In particular, the article focuses on current knowledge about its role in adult stem cells in body homeostasis as well as cancer etiology. We describe the importance of Wnt signaling in various organ systems, focusing on the role of two pivotal transcriptional co-activators of Wnt/catenin signaling, namely CBP and p300, in coordinating stem cell biology in physiology and disease. Furthermore, we are discussing the role chemical small molecules can play in orchestrating Wnt/catenin signaling and how this could be of potential benefit for regenerative medicine and novel strategies in cancer therapy.