Ion channels and transporters represent two major types of pathways of transmembrane transport for ions. Distinct from ion channels which conduct passive ionic diffusion, ion transporters mediate active transport of ions. In the perspective of biochemistry, ion transporters are enzymes that catalyze the movement of ions across the plasma membrane. In the present review, we selected the Na(+)/HCO3(-) cotransporter (NBC) as an example to analyze the key biochemical and biophysical properties of ion transporters, including stoichiometry, turnover number and transport capacity. Moreover, we provided an analysis of the electrophysiological principles of NBC based on the laws of thermodynamics. Based on the thermodynamical analysis, we showed how the stoichiometry of an NBC determines the direction of its ion transport. Finally, we reviewed the methodology for experimental determination of the stoichiometry of NBC, as well as the physiological significance of the stoichiometry of NBCs in specific tissues.