Optimization of large‐scale injection‐based remedial systems requires engineering to intentionally capitalize on the biological, chemical, and physical mechanisms that occur within and between the zones of reagent application. These types of systems can be called hybrid designs as they employ multiple processes to achieve remediation endpoints ( Figure 1 ), resulting in optimized system performance and a reduction in the overall life‐cycle cost. While all remedial applications incorporate these mechanisms to some extent, the importance of each of these processes is magnified in large‐scale applications. This column discusses the dominant mechanisms responsible for mass reduction within both source and distal plume footprints, with a focus on the application of “Hybridized Design” for enhanced reductive dechlorination (ERD) systems.