Traditionally, in vivo analysis of neurotransmitters has concentrated on the molecule dopamine and much of the surface characterization of new electrodes has been focused on the kinetics of dopamine detection. However, the field of in vivo electrochemistry is expanding to many new molecules and electrode design should follow suit to examine the extent to which it is possible to design new electrodes that have surface chemistry that is advantageous for different neurochemicals. Beyond dopamine, other small neurotransmitters that are often targeted include serotonin, norepinephrine and epinephrine. Serotonin and it’s metabolite 5-HIAA are known to foul the electrode surface of carbon fibers, but recently developed carbon nanotube-polyethyleneimine (PEI/CNT) fiber microelectrodes show reduced susceptibility for fouling. PEI/CNT fiber microelectrodes are more selective to DOPAC, and CNT yarn microelectrodes show significantly higher selectivity to serotonin than other fibers. Chlorosulfonice acid (CA)/CNT fiber microelectrodes have the highest selectivity of dopamine to ascorbic acid and uric acid, because of the negative charge carried by CA. Our lab has also investigated CNT yarn microelectrodes for adenosine detection and found that CNT yarns may be advantageous for detecting all three oxidation peaks for adenosine. In addition, we have explored surface treatments of microelectrodes, including laser treatment, oxygen plasma treatment, and antistatic gun treatment. These treatments increase the sensitivity and change the selectivity of the sensors, allowing the properties to be tuned. Thus, electrode materials, design, and surface materials are important considerations for designing in vivo microelectrodes that are sensitive to a variety of different analytes.