Bicarbonate transport occurs throughout the gastrointestinal tract and is involved in multiple functions like stability of the intestinal microclimate, secretion and absorption of electrolytes, interstitial buffering, and mucosal barrier integrity. The transporters that are involved in basolateral and apical HCO3- uptake and export are manifold and vary in the different regions of the GI tract as well as along the crypt to surface axis of the enterocytes. It is known for a decade that the expression of the CFTR anion conductance is essential for HCO3- secretion in the small intestine, whereas additional HCO3- secretory pathways exist in the colon. Recently, HCO3- secretion was shown to be important for intestinal mucin as well as Paneth cell secretion, closing the gap between the observed obstructive as well as inflammatory changes in the CF mucosa and the underlying molecular defect. Another recent major advance was the elucidation of the expression and physiological function of different SLC26anion transporters along the GI tract, and an understanding of their proven or potential involvement in disease. While mutations in Slc26a3 or DRA have been shown to cause congenital chloride diarrhea, a disease most prevalent in eastern Finland, more recent studies have shown a link between intestinal inflammation and Slc26a3 dysfunction in mice and men. Other members of the Slc26 gene family, such as Slc26a6 and Slc26a9, are also are of major importance for gastrointestinal HCO3- transport, but human diseases have not yet been linked to Slc26a6 or Slc26a9 dysfunction. Lastly, recent experiments have shed new light on the role of Na+HCO3-cotransporters and carbonic anhydrases (CAs) in gastrointestinal HCO3- transport. The recent generation of the knockout mouse for the electroneutral Na+HCO3- cotransporter NBCn1 revealed its paramount importance in duodenal HCO3-. Whereas the intracellular CAII plays an essential role in the "acid sensing" of the duodenum, the membrane- bound CAIV appears to play an import role in HCO3- transport in the lower GI tract.