Wearable potentiometric sensors have received considerable attention owing to their great potential in a wide range of physiological and clinical applications, particularly involving ion detection in sweat. Despite the significant progress in the manner that potentiometric sensors are integrated in wearable devices, in terms of materials and fabrication approaches, there is yet plenty of room for improvement in the strategy adopted for the sample collection. Essentially, this involves a fluidic sampling cell for continuous sweat analysis during sport performance or sweat accumulation via iontophoresis induction for one-spot measurements in medical settings. Even though the majority of the reported papers from the last five years describe on-body tests of wearable potentiometric sensors while the individual is practicing a physical activity, the medical utilization of these devices has been demonstrated on very few occasions and only in the context of cystic fibrosis diagnosis. In this sense, it may be important to explore the implementation of wearable potentiometric sensors into the analysis of other biofluids, such as saliva, tears and urine, as herein discussed. While the fabrication and uses of wearable potentiometric sensors vary widely, there are many common issues related to the analytical characterization of such devices that must be consciously addressed, especially in terms of sensor calibration and the validation of on-body measurements. After the assessment of key wearable potentiometric sensors reported over the last five years, with particular attention paid to those for medical applications, the present review offers tentative guidance regarding the characterization of analytical performance as well as analytical and clinical validations, thereby aiming at generating debate in the scientific community to allow for the establishment of well-conceived protocols.