The signals at the electrode-solution interface of an electrochemical nanosensor may either be dynamic or static. For dynamic methods, such as amperometric-based nanosensors that measure current proportional to the concentration of the analyte, the electroactive center of the species transfers electrons through a redox reaction at the working electrode, while in static methods the potentiometric mode of operation is followed in which charged species are involved. Nanoparticles and semiconductors have been shown to enhance the catalytic properties of analytical reactions by decreasing the overpotential of the reaction and facilitating faster electron transfer reactions, even conferring reversibility to some reactions reported to be irreversible at the unmodified electrode surfaces. Because all analytes are not intrinsically capable of serving as redox partners in electrochemical reactions, so mediators are used in these devices for facilitating the electrochemical reaction of the analytes at the electrode surface. The current chapter presents an overview of nanomaterials that affect sensing performance. Due to the attractive properties of materials at nanoscale dimensions, medical and pharmaceutical nanotechnology has become one of the most fascinating research topics in the fabrication and development of nanobiosensors. The morphology, geometric shape, and structural dimensions of materials at the nanoscale provide several advantages, which significantly influence the transduction ability of nanomaterial-modified electrodes. © 2019 Elsevier Inc. All rights reserved.