The incidence of adenocarcinoma of the esophagus has increased faster than any other internal malignancy over the last 40 years. Despite this, surprisingly little is known about the basic biology of this tissue, particularly with regards to the organization of cell proliferation within the epithelium. This is a matter of crucial importance for our understanding of the pathogenesis of esophageal cancer. Nevertheless, significant advances have recently been made in the identification and functional characterization of both murine and human esophageal stem cells and their progeny in recent years. This places investigators in an exciting position to gain further insights into the processes of tissue renewal and repair on the one hand and the development of dysplasia and malignancy on the other.