Advances in nanomaterials and nanotechnologies offer important opportunities for cellular interfaces. This Research News highlights some recent progress on cellular electrophysiology enabled by using nanostructures as active elements of bioelectronic devices. We begin with a brief description of signal transduction mechanism at device-cell interfaces and then explain the challenges of currently available techniques. Next, specific examples with substantial potential in both extracellular and intracellular electrophysiological recording are given to illustrate the remarkable power of nanostructures and their devices. We will conclude with a discussion of some exciting directions that are currently being pursued in flexible, 3D bioelectronics.