Potentiometric sensors based on ion-selective membrane electrodes have continued to get great attention from the scientific community. These sensors have been employed in several applications including medicine, forensic analysis, environmental assessment, industry, agriculture, and pharmaceutical drug analysis. Indeed these sensors possess several advantages for example simple design, fabrication, and manipulation, rapid response time, good selectivity, applicability to colored and turbid solutions, and possible interfacing with automated and computerized systems. On the other hand, therapeutic drug monitoring and detection of pharmaceutical drugs in their pharmaceutical formulations and biological matrices are highly significant from a medical point of view especially for drugs with a narrow therapeutic index such as anticancer drugs which can cause fatal side effects for patients. Interestingly, potentiometric sensors have been broadly employed as one of the most important electrochemical approaches for pharmaceutical drug analysis. Moreover, the breakthroughs in potentiometric sensors based on ion-selective electrodes (ISEs) make them superior to the other reported methods for pharmaceutical drug analysis in terms of many performance parameters such as sensitivity, selectivity, low detection limit, and low cost. In this review, we try to offer a summary prologue to the applicability and merits of the potentiometric sensors that have been employed for pharmaceutical drug analysis emphasizing their application for the assay of pharmaceutical drugs in their dosage forms and the in-vivo assay of pharmaceutical drugs in different biological samples such as milk, water, plasma, and urine.