Bioelectronics is a rapidly evolving interdisciplinary field that integrates principles of electrical engineering, materials science, and biology to develop electronic interfaces capable of recording and stimulating biological activity of the human body. The conducting polymer poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) has emerged as a key bioelectronic material due to its unique properties, processing versatility, and biocompatibility. This work provides an overview of PEDOT:PSS-based bioelectronic interfaces and their growing potential in clinical applications. The historical development of PEDOT:PSS is first traced, highlighting its rise as one of the most successful materials in organic bioelectronics. The fundamental properties that make PEDOT:PSS particularly well-suited for bioelectronic interfaces are then examined, with a focus on how these properties can be precisely tuned through advanced processing and fabrication techniques. Both well-established micropatterned interfaces and the latest advancements in multidimensional hydrogel-based structures are discussed. Finally, cutting-edge clinical applications of bioelectronic systems that incorporate PEDOT:PSS are discussed, underscoring their potential in next-generation medical technologies. Overall, this work presents a balanced and forward-looking perspective that connects the evolution of PEDOT:PSS to its emerging role in clinically translatable bioelectronic systems.