Abstract: espite progress in the management of gastrointestinal malignancies, these diseases remain devastating maladies. Conventional treatment with chemotherapy and radiation is still only partially effective and highly toxic. In the era of increasing knowledge of the molecular biology of tumors and the interaction between the tumor and immune system, the development of targeted agents, including cancer vaccines, has emerged as a promising modality. In this paper, we discuss the principals of vaccine development, and we review most of the published trials on gastrointestinal cancer vaccines that have been conducted over the last decade. Many antigens and various treatment approaches have already been tested in colon, pancreatic, and other cancers. Some of these approaches have already shown some clinical benefit. In this paper, we discuss these different strategies and some of the future directions for targeting gastrointestinal malignancies with vaccines.