Prime concerns with modern developments are attributed to high level undetected but important biological substances or even toxicants cycled often among individual and populations; which in turn agonizes environmental monitoring, trace-gas detection, water treatment facilities, in vivo detection in biological fluids and other accomplishments. For the detection of such analytes, several analytical devices combined with biological component have been designed with a physiochemical detector component. Here, we essentially focus on drug-based potentiometric membrane sensors known as ion selective electrodes (ISEs). The functionality of ion-selective membrane is quite intricate, challenging, and our understanding is yet to be thrived with more interventions. ISEs have applied explications to enormous variety of analytical inquires as well as informative tools for probing host-guest chemistry. However, expansion of ISEs based applications is aimed to improve the system performance, acquiring enhanced understanding of their response mechanism, and finding new chemical or physical configurations mainly for human welfare. The major strength of ISEs is the precised analytical information, assured by using the ion-selective membrane electrodes used successfully for both in vitro and in vivo assays of pharmaceutical products as well as in clinical analyses. In this review, we attempt to provide a brief prologue to the applicability and advantages of potentiometric sensors in the analysis of pharmaceutically active compounds emphasizing their employment at molecular level for in situ selection of biologically important analytes.