The exploration of effective methods for valorizing lignin to valuable products attracts the broad interests of a growing scientific community. Hydrodeoxygenation (HDO) of lignin-derived bio-oil is a crucial process for developing biorefineries and one of the promising ways to reduce/eliminate oxygen contents from bio-oil, which generates valuable fuels and chemicals. HDO catalysts have been discussed, including traditional HDO catalysts such as metal sulfide, metal oxide, metal phosphide, nitride, carbide, carbon-based, and zeolite-based catalysts. This chapter provides an overview of the latest progress in lignin HDO catalysts and explains the reaction mechanism that underlies the development of highly effective HDO catalysts.