The recent identification of reliable adult stem cell markers in the intestine has driven major advances in our understanding of stem cell roles in both normal tissue homeostasis and cancer. A principal route to colon cancer initiation is aberrant activation of Wnt signalling activity in long-lived adult stem cells at the crypt base. Tumour-resident stem cell populations within the resulting adenomas are considered likely targets for accumulation of additional mutations, driving a stepwise transition towards invasive carcinoma. These purported cancer stem cell populations have received widespread interest as potential therapeutic targets, fuelling efforts to identify specific biomarkers that facilitate their isolation and/or the development of tailored drugs. Here we review recent advances in (cancer) stem cell biology and highlight the obstacles to translation of this knowledge into therapeutic applications in the clinic.