In this paper, recent works on biologically coupled gate field-effect transistor (bio-FET) sensors are introduced and compared to provide a perspective. Most biological phenomena are closely related to behaviors of ions and biomolecules. This is why biosensing devices for detecting ionic and biomolecular charges contribute to the direct analysis of biological phenomena in a label-free and enzyme-free manner. Potentiometric biosensors such as bio-FET sensors, which allow the direct detection of these charges on the basis of the field effect, meet this requirement and have been developed as simple devices for in vitro diagnostics (IVD). A variety of biological ionic behaviors generated by biomolecular recognition events and cellular activities are being targeted for clinical diagnostics as well as the study of neuroscience using the bio-FET sensors. To realize these applications, bioelectrical interfaces should be formed between the electrolyte solution and the gate electrode by modifying artificially synthesized and biomimetic membranes, resulting in the selective detection of targets based on intrinsic molecular charges. Various types of semiconducting materials, not only inorganic semiconductors but also organic semiconductors, can be selected for use in bio-FET sensors, depending on the application field. In addition, a semiconductor integrated circuit device is ideal for the massively parallel detection of multiple samples. Thus, platforms based on bio-FET sensors are suitable for use in simple and miniaturized electrical circuit systems for IVD to enable the prevention and early detection of diseases.