Hypothesis-driven methods to tailor the functionality, topology, carbon orientation, and three-dimensional (3D) structure of carbon microelectrodes, for specific classes of neurochemicals, would significantly improve analyte specificity and lower the limits of detection for fast-scan cyclic voltammetry (FSCV) detection in the brain and beyond. FSCV at carbon-fiber microelectrodes is an established technique to study the signaling dynamics of many different neurochemicals in the brain. Despite its widespread applicability to many analytes, most in vivo studies are conducted on bare, unmodified carbon-fiber microelectrodes and many of the fundamental studies of new electrode materials focus on dopamine detection. Manipulations of the carbon surface can have profound effects on electrochemical detection and carefully controlled experiments to manipulate the analyte-electrode interface could provide exquisite information for future design of electrode materials. Here, we will discuss our latest work on synthesizing and manipulating the surfaces of carbon-based materials including graphene-based fibers and porous PAN-derived carbon-fiber, to exploit specific neurochemical-electrode interactions for improved detection. This presentation will demonstrate the importance of understanding the analyte-structure-electrode-surface interface for designing optimal electrodes.