Disruption of normal gastrointestinal function as a result of infection, hereditary or acquired diseases, or complications of surgical procedures uncovers its important role in acid-base homeostasis. Metabolic acidosis or alkalosis may occur, depending on the nature and volume of the unregulated losses that occur. Investigation into the specific pathophysiology of gastrointestinal disorders has provided important new insights into the normal physiology of ion transport along the gut and has also provided new avenues for treatment. This review provides a brief overview of normal ion transport along the gut and then discusses the pathophysiology and treatment of the metabolic acid-base disorders that occur when normal gut function is disrupted.