The present review compares the most diffused full-scale waste-to-energy technologies in the EU28, incineration and anaerobic digestion (AD), for exploiting the energy content of bio-waste for replacing primary energies. The comparison was performed following a life cycle approach using the cumulative energy demand index (CED) (MJ/Mg) and by the definition of the ad hoc hybrid primary energy index (HPE) (MJ/Mg), also able to account for the energy content of the waste. High values of CED for input flows for incineration were associated with auxiliary fuel consumption, up to 7000 MJ/Mg, slag disposal, about 500 MJ/Mg, and with the chemicals necessary for flue gas treatment, up to 1000 MJ/Mg. The CED values associated with electricity and heat replacement by those recovered from waste combustion ranged from about 4000 MJ/Mg up to about 24,000 MJ/Mg. The main CED associated with the input flows for AD was from maintenance of the gas engines, ranging from about 40 MJ/Mg up to 120 MJ/Mg. The CED associated with the avoided production of mineral fertilizer ranged from about 0.05 MJ/Mg to 0.7 MJ/Mg. The CED associated with electricity and heat replaced by energy recovery ranged from about 3000 MJ/Mg to about 6000 MJ/Mg. The expanded energy balance performed by the HPE (MJ/Mg) indicated that combined heat and power mode is a key factor for allowing efficient and effective replacement of primary energies by incineration. There was also a similar effect for AD but with more limited benefits. Recent research trends show a higher potential for improving the performances of AD compared to incineration.