The organic electrochemical transistor (OECT) has unique characteristics that distinguish it from other transistors and make it a promising electronic transducer of biological events. High transconductance, flexibility, and biocompatibility render OECTs ideal for detecting electrophysiological signals. Device properties such as transconductance, response time, and noise level should, however, be optimized to adapt to the needs of various application environments including in vitro cell culture, human skin, and inside of a living system. This review includes an overview of the origin of electrophysiological signals, the working principles of OECTs, and methods for performance optimization. While covering recent research examples of the use of OECTs in electrophysiology, a perspective is provided for next-generation bioelectric sensors and amplifiers for electrophysiology applications.