Biological circuits governing the behavior of individual cells, organs, or entire organisms perceive and generate a diversity of chemical, electrical, mechanical, thermal, and optical stimuli. The ability to communicate across a multitude of modalities relies on the elaborate nanoscale machinery of biomolecules and their complexes. This issue of Accounts of Chemical Research discusses the recent advances in nanoscience and electronics enabling intimate interfaces with biological circuits at scales ranging from individual proteins to organs such as the brain.