Anion exchanger proteins facilitate the exchange of bicarbonate for chloride across the plasma membrane. When bicarbonate combines with a proton it undergoes conversion into CO₂, either spontaneously, or catalyzed by carbonic anhydrase enzymes. The CO₂/HCO₃⁻ equilibrium is the body's central pH buffering system. Rapid bicarbonate transport across the plasma membrane is essential to maintain cellular and whole body pH, to dispose of metabolic waste CO₂, and to control fluid movement in our bodies. Cl⁻/HCO₃⁻ exchangers are found in two distinct gene families: SLC4A and SLC26A. Differences in the tissue distribution, electrogenicity, and regulation of the specific anion exchanger proteins allow for precise regulation of bicarbonate transport throughout the human body. This review provides a look into the structural and functional features that make this family of proteins unique, as well as the physiological significance of the different anion exchangers.