Many significant advances in our understanding of intestine development, intestinal stem cell homeostasis and differentiation have been made in recent years. These advances include novel techniques to culture primary human and mouse intestinal epithelium in three-dimensional matrices, and de novo generation of human intestinal tissue from embryonic and induced pluripotent stem cells. This short review will focus on the directed differentiation of human pluripotent stem cells into intestinal tissue, highlight novel uses of this tissue, and compare and contrast this system to primary intestinal epithelial cultures.