Anaerobic digestion is one of the technologies that will play a key role in the decarbonization of the economy, due to its capacity to treat organic waste, recover nutrients and simultaneously produce biogas as a renewable biofuel. This feature also makes this technology a relevant partner for approaching a circular economic model. However, the low biogas yield of traditional substrates such as sewage sludge and livestock waste along with high installation costs limit its profitability. Further expansion of this technology encounters several barriers, making it necessary to seek improvements to attain a favorable financial balance. The use of co-substrates benefits the overall digestion performance thanks to the balancing of nutrients, the enhanced conversion of organic matter and stabilization, leading to an increase in biogas production and process economics. This article reviews the main co-substrates used in anaerobic digestion, highlighting their characteristics in terms of methane production, kinetic models commonly used and the synergistic effects described in the literature. The main process parameters and their influence on digestion performance are presented, as well as the current lines of research dedicated to improving biogas yields, focusing on the addition of hydrogen, bioaugmentation, supplementation with carbon compounds and nanoparticles, the introduction of bioelectrodes and adsorbents. These techniques allow a significant increase in waste degradation and reduce inhibitory conditions, thus favoring process outcomes. Future research should focus on global process efficiency, making particular emphasis on the extrapolation of laboratory achievements into large-scale applications, by analyzing logistical issues, global energy demand and economic feasibility.