Analytical techniques are extensively used to assess the quality control and safety patterns in various fields of analysis. Liquid chromatography is widely used in analytical laboratories, where electrochemical detection has not been used as much as spectroscopic methods. However, its importance cannot be overlooked. Electrochemical detectors are generally versatile analytical tools with great potential that offers high sensitivity and precision in a short time, using simple and low-cost instrumentation. Among them, the potentiometry with ion-selective electrodes has been highlighted in both batch and flow analysis systems, evidenced by numerous applications performed worldwide. The determination of electrolytes in blood samples, heavy metals in natural water samples and pharmaceutical drugs in bulk drug materials are some of the representative examples. Despite the broad range of applications of ion-selective electrodes and the well-known determination of ionizable substances, references to their use as detectors in liquid chromatographic systems are scarce. Contrarily to amperometric and conductimetric detectors, which already have commercially available instrumentation to accommodate chromatographic columns, potentiometric detectors are still in an early stage. However, the results achieved so far showed the great potential development of potentiometric detectors in hydrodynamic separation systems. Therefore, it is intended to present a short view about potentiometric detection in flow analysis systems, emphasizing the case of liquid chromatography, with the purpose of enhance its importance as a tool for future process analytical applications.