Adult stem cells are crucial for normal tissue homeostasis and regeneration upon damage. Deregulated stem cell proliferation and/or differentiation have been linked to the formation and progression of tumours. Due to its high regenerative potential, the adult intestinal epithelium is an excellent system to study the mechanisms that underpin regeneration and transformation. Since the discovery of stem cell markers in the mammalian intestine – such as Lgr5 – and the presence of Drosophila intestinal stem cells there have been field-changing discoveries that have revolutionized our understanding of intestinal homeostasis, stem cells and transformation. We will thus present a brief overview of these advances with an emphasis on the role of canonical Wnt signalling and the lessons learned from genetic tractable model systems.