Because of unique immunologic and anatomic features, the results of intestinal transplantation remain significantly inferior to those associated with the transplantation of many other organs. Achieving improvements in allograft survival and function will require a more detailed understanding of the mechanisms responsible for allograft damage and the design, based on this understanding, of new strategies to better control the tissue injury resulting from organ preservation/ischemia and the recipient immune response. In this article, we review the different models that have been used to study intestinal transplantation, highlight important and/or recent results obtained using these various experimental models, and describe experimental approaches aimed at developing alternatives to allogeneic intestinal transplantation.