Ion-selective potentiometry is used more and more in clinical medicine for the determination of electrolytes in various body fluids. With regard to K+, Na+, Ca2+ and Cl- this technique has almost completely displaced flame photometry, atomic absorption spectrophotometry and coulometry. Moreover, reliable automated devices have facilitated routine analyses. Until now there are 6 different types of ion-selective sensors: glass membrane, solid phase, fluid membrane, carrier, gas-sensitive, and enzyme electrodes with immobilized enzymes. The latter are particularly used for in vivo monitoring, especially for continuous blood glucose monitoring. The essential fields of application in the clinical laboratory are the determinations of the cations H+, K+, Na+, Ca2+, Mg2+ and NH3+, and the anions F-, I-, Br-, Cl- and HCO3-. Despite the wide-spread application of ion-selective potentiometry a number of disturbing factors have to be taken into account by the user as well as by the manufacturer in order to get satisfactory results. For instance, there are differences between direct and indirect potentiometry. Moreover, the activities measured cannot be extrapolated readily to the desired concentrations. A careful and accurate calibration, a suitable sample preparation and an adjustment of the measuring conditions to the characteristics of the specimen and the matrix of the sample is necessary before each measurement. Therefore, a consequent internal and external quality control is necessary to achieve an optimal quality of these methods determining vital parameters in medicine. Thus, the technique of ion-selective potentiometry represents an important milestone in clinical chemistry. Moreover, being a very rapid procedure it is indispensable to clinical diagnostics.