In several geographic areas, domestic wastewater (DWW) is characterized by low temperatures (below 25°C), which enables a stable and effective operation of an anaerobic process, as mainstream treatment option at ambient temperature, quite challenging. Low temperatures reduce the hydrolysis rate of particulate organic matter with consequent reduction of biogas production and energy recovery. In addition, the low growth rate of the anaerobic microorganisms can cause poor effluent quality and risk of biomass washout in case of suspended biomass systems. Increasing biomass concentration in the bioreactor has the beneficial effect of increasing biodegradation kinetics thus allowing the reduction of the reactor volumes and footprint thus making the anaerobic process competitive with the conventional activated sludge process. This operating condition can be achieved with different strategies including biomass granulation and biomass immobilization on inert support media. For both alternatives, a number of studies have been conducted, with different plant configurations, operating the anaerobic process under variable temperature regimes or in isothermal mode in psychrophilic or mesophilic conditions. In this chapter, examples of application to demonstrate the feasibility of immobilized and granular biomass systems for direct anaerobic treatment of DWW are reported and discussed. In the first case, the effect of feeding strategy and the suitability of natural and synthetic filling materials were investigated while, in the second, the effect of temperature and of the hydraulic retention time have been tested in order to maximize the process performance and evaluate the potentialities of the anaerobic process in comparison to the aerobic one.