Therapeutic radiation for cancer is more than 100 years old. Side effects constitute the main limitation to its use. Side effects may be acute or chronic, but these categories overlap. As cancer survival improves, chronic radiation damage becomes more common. The gastrointestinal (GI) tract, particularly the bowel, is particularly vulnerable because of its anatomical location and the rapidity of turnover of many GI epithelial cell types. Severity of radiation damage depends also on patient factors, chemotherapy, radiotherapy regimen, and organ mobility. Histologically, common mucosal changes include ulceration, acute inflammation, eosinophilic infiltrates, and architectural abnormalities. Fibrosis may occur later. Vascular changes are more common in chronic disease, affect deeper layers, and include ectasia, intimal thickening, fibrinoid change, thrombosis, and luminal obliteration. Atypia of epithelium, fibroblasts, and endothelium is common and can mimic neoplasia. Epithelial atypia has a lower nuclear:cytoplasmic ratio than dysplasia and matures towards the mucosal surface, aiding the distinction. Features sometimes resemble viral cytopathic change. Chronic radiation colitis may resemble inflammatory bowel disease, ischaemia, and mucosal prolapse while vascular changes may resemble amyloid. In summary, histological clues to radiation damage include fibrosis, atypical fibroblasts, eosinophilic infiltrates, and vascular changes. Confident diagnosis as radiation damage requires a clinical history but this may be unavailable, especially if decades have elapsed since therapy.