Diseases of the gastrointestinal tract that require pharmacologic management, usually in combination with other treatments, are gastric ulcers (omeprazole and others), colic (laxatives, analgesics), diarrhea (antibiotics, protectants and absorbents, glucocorticoids, motility inhibitors), reperfusion injury, postoperative ileus (prokinetic drugs), and adhesions. There is growing evidence that nonsteroidal anti-inflammatory drugs can alter important physiologic properties of the intestine; however, these drugs are valuable analgesics for horses and their use should be tempered with an awareness of their harmful effects. The role of antibiotics in treating gastrointestinal disease is controversial, but their ability to induce life-threatening diarrhea is well known and invites caution and defensible use of these drugs in horses.