Recent studies have shown that anaerobic co-digestion (AnCoD) is superior to conventional anaerobic digestion (AD). The benefits of enhanced bioenergy production and solids reduction using co-substrates have attracted researchers to study the co-digestion technology and to better understand the effect of multi substrates on digester performance. This review will discuss the results of such studies with the main focus on: (1) generally the advantages of co-digestion over mono-digestion in terms of system stability, bioenergy, and solids reduction; (2) microbial consortia diversity and their synergistic impact on biogas improvement; (3) the effect of digester mode, i.e., multi-stage versus single stage digestion on AnCoD. It is essential to note that the studies reported improvement in the synergy and diverse microbial consortia when using co-digestion technologies, in addition to higher biomethane yield when using two-stage mode. A good example would be the co-digestion of biodiesel waste and glycerin with municipal waste sludge in a two-stage reactor resulting in 100% increase of biogas and 120% increase in the methane content of the produced biogas with microbial population dominated by Methanosaeta and Methanomicrobium.