Since their original identification in Drosophila, the caudal related homologues (Cdx1 and Cdx2) have been known to be evolutionarily conserved both in molecular structure and function. In a great variety of organisms they are recognized to function critically during antero-posterior patterning and the development of the intestinal epithelium. The Cdx homologues, when expressed, modulate a diverse set of processes including proliferation, apoptosis, cell-adhesion, and columnar morphology. They are also necessary for the expression of an increasing number of intestine-specific genes. By targeting these processes and genes, the Cdx homologues promote the appearance of a mature intestinal cell phenotype. In addition to these critical roles during development, accumulating evidence suggests that the Cdx homologues may play significant roles in oncogenesis in the gastrointestinal tract and other tissues. In the colon, several studies suggest the Cdx homologues may act as tumor suppressors. However, ectopic Cdx1 and Cdx2 expression is involved in the development of the precancerous intestinal metaplasia in the stomach and esophagus, and may be a transforming event in one form of acute myelogenous leukemia. This review will explore our current understanding of the roles of the caudal homologues Cdx1 and Cdx2 in intestinal development and carcinogenesis.