Carbon nanotubes (CNTs) have attracted great interdisciplinary interest due to their peculiar structural, mechanical and electronic properties. Applications of CNTs in biomedical research are being actively explored by many scientists worldwide. However, manipulation of CNTs is impeded by several problems, such as 1) formation of complex and entangled bundles; 2) very low solubility of CNTs in organic solvents and water; 3) inert properties of pristine CNTs under many chemical reaction conditions, etc. Chemical modification of CNTs has partly solved the above issues and is still one of the most effective means of manipulating and processing CNTs. Many bioapplications of CNTs rely on successful outer/inner surface functionalizations. This Feature Article is comprised of two main parts. In the first part, we briefly review the covalent surface chemistry for the CNT functionalization; in the second part, we focus on the biomedical applications of surface chemistry for CNTs, in particular, the chemistry for controlling biomedical functions and meanwhile lowering nanotoxicity of CNTs. We also analyze the underlying factors that led to the controversy in the previous experimental data of safety studies of CNTs.