The purpose of the present review is to describe the use of carbonic anhydrase inhibitors in clinical medicine and renal physiology. We first describe the localization of carbonic anhydrase within the kidney and then discuss evidence for its role in renal acidification and NaCl absorption. This is then followed by a description of clinical uses for carbonic anhydrase inhibitors. Many of the uses and effects of carbonic anhydrase inhibitors can be predicted from an understanding of renal physiology and the role of carbonic anhydrase. The limited potency of carbonic anhydrase inhibitors correlates well with the large magnitude of carbonic anhydrase-independent bicarbonate absorption. While theories for carbonic anhydrase-independent bicarbonate absorption are presented, the exact mechanisms remain unresolved.