Integration of external electronics and the nervous system has immense potential to advance human understanding of the nervous system and the brain. A neural interface is an engineered device designed to exchange information with the nervous system. The peripheral nervous system (PNS) relays information to and from the central nervous system (CNS), comprising the brain and spinal cord. Advances in cuff design attempt to counter the challenging three-dimensional geometry of the fascicle by changing the geometry. Interfacing to the central nervous system itself involving the brain and spinal cord is now a major focus of neuro-engineering. When a device is implanted in the brain or spinal cord for extended periods, an unforgiving inflammatory response is initiated. The intimacy and density of neural interfaces promises to be dramatically increased by connections between microcircuits and single neurons or even single ion channels.