Many operating parameters, individually or together, may influence the performance of anaerobic digestion towards biogas or digestate yield and quality maximization. The most preferred method of optimizing an anaerobic digestion plant often relies on how carefully the crucial parameters, such as pH, temperature, organic loading rate, hydraulic retention time, and pressure, are chosen. There is a large amount of literature available on optimization of anaerobic digestion; however, given the continued development and implementation of innovative technologies, together with the introduction of increasingly complex systems, it is necessary to update present knowledge on process parameters and their role on operational ranges and flexibilities in real-life anaerobic digestion system. Accordingly, the present review discusses the importance of the selection of operational parameters in existing technologies and their impact on biogas yield. Notably, the four broad areas of feedstock utilization (substrate, inoculum, codigestion and pretreatment), process condition (pH, temperature, pressure, and reactor design), reactor control (HRT and OLR) and inhibition (Ammonia and VFAs) are covered in this review. In addition, particular emphasis is placed on the most recent innovations that have been or may be implemented in current or future biogas plants.