The organic electrochemical transistor (OECT) has emerged as the core component of specialized bioelectronic technologies, such as neural interfaces and sensors of disease biomarkers. At the heart of the OECT is its channel, made of an organic mixed ionic–electronic conductor (OMIEC). The chemical structure of the OMIEC governs the electronic, optical and mechanical traits of OECT, with even subtle structural tweaks leading to sizeable functional disparities. In this Review, we summarize the recent progress in OECT device development while underscoring the critical role of OMIEC selection in steering diverse applications. Our narrative charts the milestones in materials exploration, tracing the evolution of the field in parallel with polymer chemistry breakthroughs. We emphasize how materials design has enabled new device operation mechanisms by adding features such as biocompatibility, stretchability, stimuli response and memory retention to OMIECs. We also highlight the obstacles that must be surmounted to translate OECT-based devices from laboratory instruments into tangible real-world technologies.