Carbon nanotubes, graphenes, and their hybridized composites with nanoparticles have been attempted to establish a direct electrical communication between the recognition biomolecule and its underlying electrode surface. This review (with 133 refs.) focuses on advances, strategies and technical challenges in the development of reagentless electrochemical biosensors for glucose with enhanced detection sensitivity, selectivity, and simplicity. Specifically, the review commences with a discussion of the relevance of direct electron transfer (DET) in biosensing together with the fundamental of electro-enzymology and kinetics. General aspects of glucose oxidase (GOx), the most popular enzyme with a flavin cofactor, are discussed in view of its historical and important role in the development of electrical biosensors for blood glucose. The next section assesses DET of GOx based on the Marcus theory and the Laviron formalism. The reorganizational energy of the Marcus model and the overpotential play an important role in reaction kinetics and affect the rate of electron transfer significantly. The presence of nanomaterials, particularly for graphene oxide, decreases the electron transfer distance between the enzyme redox center and the underlying electrode surface well beyond 15 . The improper Marcus-Hush-Chidsey integral is now simplified to estimate the rate of electron transfer with very good accuracy. Critiques, technical challenges, and future possibilities of glucose electrodes with respect to DET are also presented and discussed.