Graphene possesses a high surface-to-volume ratio, which enables biomolecules to attach to it for bioelectronic applications. In this article, first, the classification and applications of bioelectronic devices are briefly reviewed. Then, recent work on real fabricated graphene-based bioelectronic devices as well as the analysis of their architecture and design using a computational approach to their charge transport properties are presented and discussed. A comparison to nongraphitic bioelectronic devices is also given. On the macroscale level, the design of devices is elaborated on the basis of a finite element analysis (FEA) approach, and the impact of design on the performance of the devices is discussed. On the nanoscale level, transport phenomena and their mechanisms for different design categories are elaborated on the basis of the density functional theory (DFT) and other quantum chemistry calculations. The calculated and measured charge transport properties of graphene-based bioelectronic devices are also compared with those of other available bioelectronic devices.