Efficient thermochemical conversion of ligno-cellulosic biomass towards compatible liquid fuels like diesel and gasoline, potentially alcohols and ethers, is a story about new opportunities and challenging chemistry. Innovations of enabling materials (catalysts, adsorbents, membranes), efficient processing schemes, robust products portfolios and smart business strategies are needed to close the priority gap between fossil and the more complex renewable resources. Co-production of (platform) chemicals and bio-products can improve the economical basis. Options for thermochemical processing towards fuels include the pyrolysis route, which is proceeding via bio-oil (BO) upgrading, and the alternative gasification route, which is proceeding via syngas followed by catalytic synthesis, e.g. Fischer-Tropsch. The number of conditioning and conversion steps that can be envisaged along both routes needs to be minimized. Basic pretreatment of raw BO is chemical stabilization, which enables its storage or transport. More advanced upgrading is required to reach oil qualities suitable for heat and power, and even more advanced for transport applications (including aviation fuel). Catalysts and hydrogen can provide the required processing flexibility and product quality. Catalytic hydrodeoxygenation (HDO) is one of the most attractive upgrading options, enabling removal of heteroatoms, adding energy, and chemical transformations for tuning of properties. This review focuses on HDO and the catalytic properties of metal carbides, nitrides and phosphides, the potential of mesoporous-based catalytic materials, and also of noble metals. An overview of matured hydrotreating (HT) technology and conventional catalysts for HDS is provided as the benchmarking technology for developments towards increased biomass utilization.