Disruption of normal bowel function as a result of infection, inflammation, complications of surgical procedures, or hereditary and acquired transport abnormalities uncovers its critical importance for acid-base, electrolyte, and fluid volume homeostasis. The nature of the acid-base disorder that develops is directly dependent on the electrolyte composition of the fluid that is lost as well as by the magnitude of the losses. Regardless of whether metabolic acidosis or alkalosis develops, the disorder is sustained only when the losses are large enough to impair renal homeostatic mechanisms and maintenance of fluid and electrolyte balance through increased oral intake. The mainstay of the acute treatment for all sustained disorders of acid-base equilibrium that are induced by abnormal gastrointestinal losses is vigorous extracellular fluid volume repletion, with appropriate adjustments in the electrolyte composition of the replacement fluids to reflect specific losses. The long-term approach is to correct the underlying gastrointestinal disorder if possible. Our hope is that advances in our understanding of ion transport along the gut will provide new avenues for the treatment of disorders that disrupt its function. Gastrointestinal disorders provide an experiment in nature that has shed light on the normal transport properties of the gut as well as uncovered its importance in acid-base and electrolyte homeostasis.