The gastrointestinal epithelium is a unique model for the study of mammalian stem cells. Not only does it have a highly stereotypical organization, its remarkable rate of self-renewal provides a daily readout of stem cell activity. The past decade has seen a major investment in developing technologies dedicated to revealing the identity of the long-elusive gastrointestinal stem cells. An array of purported stem cell biomarkers is now available for the mouse, including surface-expressed proteins that hold great promise as antibody targets for use in isolating human stem cells. Here we critically appraise the validity of these biomarkers and discuss their likely impact on our understanding of stem cell roles in self-renewal and cancer in the gastrointestinal tract.