Fast pyrolysis of biomass is an attractive approach for the densification of its energy content. Through this approach, biomass is transformed into liquids (bio-oils or pyrolysis oils) having a considerable oxygen content. Therefore, upgrading is required to convert oxygenates into hydrocarbons, improving the oil properties and broadening the application range. In this instance, catalytic hydrotreatment was demonstrated to be an attractive technology for the upgrading of fast pyrolysis oil into stabilized products. This chapter presents an overview on the typical features of the hydrotreatment process (e.g. reaction conditions, catalysts, product yields, deoxygenation levels, product properties, analytical methods, and reaction pathways). Finally, recent results for a catalytic hydrotreatment process in the presence of a novel Ni–Cu catalyst supported on SiO2 will be discussed. Regarding catalyst performance and properties of the product oil, this catalyst shows considerable advantages over the benchmark Ru/C catalyst.