The site-specific surface modification of colloidal substrates, yielding "patchy" nanoparticles, is a rapidly expanding area of research as a result of the new complex structural hierarchies that are becoming accessible to chemists and materials scientists through colloidal self-assembly. The inherent directionality of cellulose chains, which feature a non-reducing and a reducing end, within individual cellulose nanocrystals (CNCs) renders them an interesting experimental platform for the synthesis of asymmetric nanorods with end-tethered polymer chains. Here, we present water-tolerant reaction pathways toward patchy and uniformly modified CNC hybrids based on atom transfer radical polymerization (ATRP) and initiators that were linked to the CNCs with carbodiimide-mediated coupling and Fischer esterification, respectively. Various monomers, including Nisopropylacrylamide (NIPAM), [2-(methacryloyloxy)ethyl]trimethylammonium chloride (METAC), and sodium 4vinylbenzenesulfonate (4-SS) were polymerized from both types of initiator-modified CNCs, yielding chemically patchy and uniform CNC hybrids, via surface-initiated ATRP (SI-ATRP). Interestingly, the stereochemistry of tethered PNIPAM was affected by the precise location of ATRP initiating sites, as evidenced by 1 H NMR and circular dichroism (CD) spectroscopy. This effect may be related to the inherent right-handed chirality of CNCs. CNC/PMETAC hybrids were labeled with gold nanoparticles (AuNPs) in order to visualize the precise location of polymer tethers via cryo-electron microscopy. In some instances, the AuNPs were indeed concentrated at the end groups of the patchy CNC hybrids.The site-specific surface modification of colloidal substrates, yielding "patchy" (nano)particles, is receiving rapidly expanding interest, as a result of the new complex structural hierarchies that are becoming accessible to chemists and materials scientists through colloidal self-assembly. 1 Such patchy particles include Janus colloids, 2 genetically engineered bacteriophages, 3,4 cylindrical block copolymer micelles, 5 and polymer-tethered nanorods. 6 Particle shape anisotropy provides additional building block parameters, which can broaden the complexity of their assemblies. 7 The lyotropic liquid crystal formation capability of rod-shaped colloidal building blocks is an excellent example of such a self-assembly process. 8 In special cases, these liquid crystal (LC) phases exhibit longrange chirality, displaying so-called cholesteric or chiral nematic arrangements, which are not only fundamentally intriguing for condensed matter investigations, 9 but also useful as chiral building blocks for the creation of advanced functional materials. 10 Relatively few anisotropic colloids that exhibit such chiral phases are known; they include filamentous viruses, 11 collagen, 12 chitin, 13 and cellulose nanocrystals (CNCs). 14 CNCs are a unique class of colloidal liquid crystals in that their cholesteric LC phases are preserved upon evaporation-induced self-assembly (EISA), which together with ...