The diverse cellular lineages that populate the intestinal epithelium are derived from committed stem cells located in intestinal crypts. The complex architecture of the intestinal epithelium results from well-orchestrated processes of cell-line-age allocation, proliferation of immature cells in the crypt compartment, differentiation of various cell lineages, migration of cells in defined patterns, and cell-specific programmed senescence. The patterns of intestinal gene transcription in the context of this complex architecture are regulated by the combinatorial effect of multiple positive and negative regulatory elements. Although the DNA regulatory elements required to recapitulate the pattern of endogenous gene expression appear to be spread over relatively large genomic distances, short promoters of several intestinal genes are sufficient to direct intestine-specific transcription. The sucrase-isomaltase gene promoter has multiple regulatory elements that bind tissue-restricted transcription factors. A critical factor in regulating the sucrase-isomaltase promoter is Cdx2, an intestine-specific homeobox gene related to caudal, that may also have a broader role in intestinal development and morphogenesis. As additional regulatory elements and their cognate DNA-binding proteins are identified, the challenge will be to define their integrated role in the regulation of intestine-specific genes and in the development and maintenance of the intestinal epithelium.