The anaerobic digestion technology has been in existence for centuries and its underlying theory established for decades. It is considered a useful technology for the generation of renewable energy, and provides means to alleviate problems associated with low access to energy. However, a great deal of current research is targeted towards the optimization of this technology under diverse digestion process conditions. This review presents an in-depth analysis of the chemistry of anaerobic digestion and discusses how process chemistry can be used to optimize system performance through identification of methods that can accelerate syntrophic interactions of different microorganisms for improved methanogenic reactions. Recent advances in addition to old research are discussed in order to offer a general but comprehensive synopsis of accumulated knowledge in the theory of anaerobic digestion, as well as an overview of previous research and future directions and opportunities of the AD technology. Achieving a sustainable energy system requires comprehensive reforms in not just economic, social and policy aspects, but also in all technical aspects, which represents one of the most crucial future investments for anaerobic digestion systems.