Gastrointestinal cancers comprise multiple malignancies with diverse etiologies arising from distinct subsites of the squamous and glandular epithelium of the gastrointestinal (GI) tract. Radiation therapy is an integral part of the established treatment paradigm for many of them. RT serves as the definitive modality for some (anal cancer) and as an adjuvant/neoadjuvant (esophageal and rectal cancer) or a primarily palliative for others. Moreover, the role for RT in the management of some GI malignancies is less established, either due to the relative rarity of the disease and paucity of data (cholangiocarcinoma), availability of multiple therapeutic alternatives (hepatocellular carcinoma), or changing data landscape regarding the efficacy of RT (pancreatic cancer). This chapter will systematically address the salient features of diagnosis and management of each sub-site, focusing on patient selection for RT and RT planning. Important emerging themes include organ preservation, which started with anal cancer, has now gained acceptance in rectal cancer and is being investigated for esophageal cancer, as well as dose escalation as a definitive treatment. Advanced technologies, including proton therapy, SBRT, and MRgRT, play an important role in a small number of clinical settings and will be specifically discussed where appropriate.