Hydrodeoxygenation (HDO) of guaiacol (GUA), a lignin model compound, was examined by two types of catalysts: mono- and bimetallic Rh based catalysts and classical sulfided CoMo and NiMo catalysts. The former possessed greater reactivity than the latter. However, no positive effect could be found when substituting some of the Rh ions by another noble metal (i.e., Pd or Pt). The mechanisms of GUA HDO by these two types of catalysts were also proposed. The first step of Rh based catalysts was hydrogenation of GUA's benzene ring, proceeded by demethoxylation and dehydration. As for the sulfided CoMo and NiMo catalysts, the reaction steps were just the reverse: dehydration and demethoxylation first, followed by further hydrogenation. Future improvements in understanding HDO surface chemistry can possibly lead us to design efficient catalysts for target products.