This review deals with the structure of the active phase in sulfidic Co-Mo and Ni-Mo hydrotreating catalysts. Various models describing the catalyst and its interaction with the reaction environment are discussed in the light of the evolution of the active phase during the catalyst life cycle. Special attention is paid to the contribution of Mossbauer Emission Spectroscopy (MES), Extended X-ray Absorption Fine Structure (EXAFS), High Resolution Transmission Electron Microscopy (HR-TEM) and Molecular Modeling to the unraveling of the active phase structure. It is concluded that MoS2 sintering and Co9S8 (Ni3S2, NiS) segregation during the catalyst life cycle force the shift of the actual reaction mechanism from that involving a single site or an ensemble of sites to that of a close cooperation between segregated components. The adsorption of reactants can take place in many different ways, through the heteroatom or through the ring, on the Mo sites as well as on the Co (Ni) sites. The exact state of each active site depends on the reaction environment. If the catalyst is S deficient, the classical adsorption mechanism involving the S vacancy is dominant. With a fully sulfided catalyst surface the adsorption takes place through S-S bonds. The catalyst is a dynamic evolving system adapting itself to its ever changing reaction environment. Each catalyst component fulfills multiple functions in determining the catalyst structure as well as its interaction with the reactant molecules.