The epithelium of the adult mammalian intestine is in a constant dialog with its underlying mesenchyme to direct progenitor proliferation, lineage commitment, terminal differentiation, and, ultimately, cell death. The epithelium is shaped into spatially distinct compartments that are dedicated to each of these events. While the intestinal epithelium represents the most vigorously renewing adult tissue in mammals, the stem cells that fuel this self-renewal process have been identified only recently. The unique epithelial anatomy makes the intestinal crypt one of the most accessible models for the study of adult stem cell biology. This review attempts to provide a comprehensive overview of four decades of research on crypt stem cells.