Organic bioelectronic sensors are gaining momentum as they can combine high-performance sensing level with flexible large-area processable materials. This opens to potentially highly powerful sensing systems for point-of-care health monitoring and diagnostics at low cost. Prominent to detect biochemical recognition events, are electrolyte-gated organic field-effect transistors (EGOFETs) and organic electrochemical transistors (OECTs) as they are easily fabricated and operated. EGOFETs are recently shown to be capable of labelfree single-molecule detections, even in serum. This progress report aims to provide a critical perspective through a selected overview of the literature on both EGOFET and OECT biosensors. Attention is paid to correctly attribute them to the potentiometric and amperometric biosensor categories, which is important to set the right conditions for quantification purposes. Moreover, to deepen the understanding of the sensing mechanisms, with the support of unpublished data, focus is put on two among the most critical aspects, namely, the capacitance interplay and the role of Faradaic currents. The final aim is to provide a rationale of the functional mechanisms encompassing both EGOFET and OECT sensors, to improve materials and devices' designs taking advantage of the processes that enhance the sensing response enabling the extremely highperformance level resulting in ultimate sensitivity, selectivity, and fast response.