The long retention time of the active biomass in the high-rate anaerobic digesters is the key factor for the successful application of the high rate anaerobic wastewater treatment. The long solids retention time is achieved due to the specific reactor configuration and it is enhanced by the immobilization of the biomass, which forms static biofilms, particle-supported biofilms, or granules depending on the reactor's operational conditions. The advantages of the high-rate anaerobic digestion over the conventional aerobic wastewater treatment methods has created a clear trend for the change of the role of the anaerobic digestion in the wastewater treatment plants from a pre-treatment method to the main biological treatment method. The application of staged high-rate anaerobic digesters has shown the larger potential among the recent developments in this direction. The most common high-rate anaerobic treatment systems based on anaerobic granular sludge and biofilm are described in this chapter. Emphasis is given to a) the Up-flow Anaerobic Sludge Blanket (UASB) systems, b) the main characteristics of the anaerobic granular sludge, and c) the factors that control the granulation process. Finally, the most innovative staged anaerobic digesters are also presented.