We have reviewed the basic aspects of history, physicochemical properties, advantages, disadvantages, and applications of nystatin- and amphotericin B-perforated patch recording. Recently, we have developed a novel perforated patch technique using gramicidin [49, 132, 133]. Since gramicidin pores are permeable to Na+ and K+ but not to Cl-, it is possible to maintain the physiological concentration of intracellular Cl- and thereby to measure it in real-time from small neurons. Further improvement of the perforated patch techniques would be possible by limiting redistribution of specific intracellular ions. In light of their broad applicability, the perforated patch techniques will prove indispensable for electrophysiologists working on the functions and modulations of receptors, ion channels and transport phenomena. Research with the perforated patch should continue to provide important information relevant to the physiological and pathological conditions of cells.