The rising field of bioelectronics, which couples the realms of electronics and biology, holds huge potential for the development of novel biomedical devices for therapeutics and diagnostics. Organic electronic devices are particularly promising; the use of robust organic electronic materials provides an ideal biointerface due to their reported biocompatibility, and mechanical matching between the sensor element and the biological environment, are amongst the advantages unique to this class of materials. One promising device emerging from this field is the organic electrochemical transistor (OECT). Arguably, the most important feature of an OECT is that it provides local amplification and as such can be used as a high fidelity transducer of biological events. Additionally, the OECT combines properties and characteristics that can be tuned for a wide spectrum of biological applications. Here, we frame the development of the OECT with respect to its underlying optimization for a variety of different applications, including ion sensing, enzymatic sensing, and electrophysiology. These applications have allowed the development of OECTs to sense local ionic/biomolecular and single cell activity, as well characterization of tissue and even monitoring of function of whole organs. The body of work reviewed here demonstrates that the OECT is an extremely versatile device that emerges as an important player for therapeutics and diagnostics. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41735.