Biological systems have evolved biochemical, electrical, mechanical, and genetic networks to perform essential functions across various length and time scales. High-aspect-ratio biological nanowires, such as bacterial pili and neurites, mediate many of the interactions and homeostasis in and between these networks. Synthetic materials designed to mimic the structure of biological nanowires could also incorporate similar functional properties, and exploiting this structure-function relationship has already proved fruitful in designing biointerfaces. Semiconductor nanowires are a particularly promising class of synthetic nanowires for biointerfaces, given (1) their unique optical and electronic properties and (2) their high degree of synthetic control and versatility. These characteristics enable fabrication of a variety of electronic and photonic nanowire devices, allowing for the formation of well-defined, functional bioelectric interfaces at the biomolecular level to the whole-organ level. In this Focus Review, we first discuss the history of bioelectric interfaces with semiconductor nanowires. We next highlight several important, endogenous biological nanowires and use these as a framework to categorize semiconductor nanowire-based biointerfaces. Within this framework we then review the fundamentals of bioelectric interfaces with semiconductor nanowires and comment on both material choice and device design to form biointerfaces spanning multiple length scales. We conclude with a discussion of areas with the potential for greatest impact using semiconductor nanowire-enabled biointerfaces in the future.