The intestinal epithelium is structured in crypt-villus units which are responsible for its continuous renewal. These units are organized in a dynamic scenario in which proliferating progenitor cells are generated from stem cells in the crypts and migrate along the villus axis until their extrusion as differentiated cells at the surface epithelium. The mechanisms controlling cell transition involve transcription factors that switch on and off compartment-specific genes. The Wnt cascade represents the dominant force controlling cell fate in the crypt-villus axis. Mutations in this cascade result in the development of colorectal cancer. Life-style modifications and dietary regimens are epidemiologically recognized contributing factors for intestinal tumorigenesis. Nuclear receptors are a family of transcription factors functioning as sensors of dietary and endogenous molecules, thus translating nutritional and hormonal stimuli into transcriptional modifications. This review presents the role of nuclear receptors in intestinal carcinogenesis and explores their influence in maintenance of intestinal epithelium architecture.