This chapter explores one modality of using carbon nanofibers in biointerfacing, that is, via mechanical properties. Vertically aligned carbon nanofibers (VACNF), stacked cylinders of graphitic carbon, possess many properties that make them attractive structures for implementation as interfaces to biological systems on a cellular level or subcellular level. In biosensing both selectivity, that is, the ability to distinguish between molecular species, and sensitivity, that is, the signal amplitude, are important for signal detection. The selectivity of graphitic carbon can be achieved in two ways. VACNFS are synthesized using metal catalyst particles. Understanding of catalytic synthesis has seen many advances since early transmission electron microscopy images of Fe nanoparticles at the ends of the carbon fibers. The most commonly used catalyst nanoparticles are Ni, Fe, and Co. Chemical vapor deposition allows for the growth of CNFs, but only PECVD has been demonstrated to obtain deterministically grown vertically aligned CNFs, necessary for most biological applications.