Acid-related disorders including esophagitis and gastroduodenal ulceration are uncommon in the cat. However, when they occur, they can have devastating consequences and require targeted intervention, including the use of gastroprotectants. Careful consideration of the causes of esophagitis and gastroduodenal ulceration can help the clinician to determine which gastroprotectant to use, and when to begin and end gastroprotective therapy. Gastroprotectants remain one of the most misused classes of drugs in veterinary and human medicine. There are very few studies evaluating the efficacy of gastroprotective agents in cats. Furthermore, goals for the degree of gastric acid suppression are extrapolated from studies performed in dogs and humans. This review provides a foundation for the logical approach to the choice of gastroprotectant as indicated by the disease process, and is aimed at all veterinarians who prescribe gastroprotectants for use in cats. The guidance provided in this review is supported by current literature, including consensus opinion from the American College of Veterinary Internal Medicine. Gaps in evidence for use of gastroprotectants in cats are filled by extrapolations from studies performed in dogs and humans.