The microelectrode technique is today the most widely used method in electrophy- siology. Microelectrodes offer a unique approach to measurements of electrical pa- rameters and ion activities of single cells. Several important breakthroughs in trans- port physiology have arisen from microelectrode studies. Undoubtedly, there is a progressively wide-spread use of conventional and ion-selective microelectrodes. Due to their particular dimension and properties micro electrodes are exclusive- ly applied to measurements on living matter. This must have many consequences to my thoughts on experiments with microelectrodes. In this book, my concern is fo- cussing on the description of an intracellular method that should lead to reliable in- formation on cellular parameters. The methodical basis for any meaningful applica- tion is treated extensively. However, technical perfection and accurate results are not the only concern when working on animals and human beings. Rather, my thoughts are governed by the intellectual and moral mastery of the experimental ap- proach on living subjects. A measurement with microelectrodes usually necessitates the sacrifice of an ani- mal. This is an immense fact, and means that the knowledge gained by the experi- ment must justify the death of a living subject.