The unique properties of nanoscale materials offer excellent prospects for interfacing biological recognition events with electronic signal transduction and for designing a new generation of bioelectronic devices exhibiting novel functions. In this Highlight I address recent research that has led to powerful nanomaterial-based electrical biosensing devices and examine future prospects and challenges. New nanoparticle-based signal amplification and coding strategies for bioaffinity assays are discussed, along with carbon-nanotube molecular wires for achieving efficient electrical communication with redox enzyme and nanowire-based label-free DNA sensors.