Biosensing plays vital roles in multiple fields, including healthcare monitoring, drug screening, disease diagnosis, and environmental pollution control. In recent years, transistor-based devices have been considered to be valid platforms for fast, low-cost sensing of diverse analytes. Without additional functionalization, however, these devices lack selectivity; several strategies have been developed for the direct immobilization of bioreceptors on the transistor surface to improve detection capabilities. In this scenario, organic transistors have gained attention for their abilities to be coupled to biological systems and to detect biomolecules. In this Perspective, we discuss recent developments in organic-transistor-based biosensors, highlighting how their coupling with artificial membranes provides a strategy to improve sensitivity and selectivity in biosensing applications. Looking at future applications, this class of biosensors represents a breakthrough starting point for implementing multimodal high-throughput screening platforms.