Heterogeneous interfaces that are ubiquitous in optoelectronic devices play a key role in the device performance and have led to the prosperity of today's microelectronics. Interface engineering provides an effective and promising approach to enhancing the device performance of organic field-effect transistors (OFETs) and even developing new functions. In fact, researchers from different disciplines have devoted considerable attention to this concept, which has started to evolve from simple improvement of the device performance to sophisticated construction of novel functionalities, indicating great potential for further applications in broad areas ranging from integrated circuits and energy conversion to catalysis and chemical/biological sensors. In this review article, we provide a timely and comprehensive overview of current efficient approaches developed for building various delicate functional interfaces in OFETs, including interfaces within the semiconductor layers, semiconductor/electrode interfaces, semiconductor/dielectric interfaces, and semiconductor/environment interfaces. We also highlight the major contributions and new concepts of integrating molecular functionalities into electrical circuits, which have been neglected in most previous reviews. This review will provide a fundamental understanding of the interplay between the molecular structure, assembly, and emergent functions at the molecular level and consequently offer novel insights into designing a new generation of multifunctional integrated circuits and sensors toward practical applications.