Over the past decade, we have learned a number of critical lessons surrounding carbon substrate handling while operating and maintaining hundreds of enhanced in situ biological remedies. The same qualities that make these substrates effective can also cause biofouling of the mixing system, piping infrastructure, and remediation wells. Managing biofouling is a key piece of a successful remedy and requires a unique set of design principles. Small decreases in injection rates can have considerable impacts to life-cycle costs and performance caused by decreased substrate distribution and longer injection time frames, resulting in the need for system cleaning, well rehabilitation, and even well replacement. Biofouling can impair performance in any size system, but effects are often magnified by large injection volumes and extended time frames. Design should be considered in all stages of the anaerobic enhanced in situ bioremediation life cycle, particularly related to reagent mixing, storage, and residence time within the system. By understanding the fundamental mechanisms of biofouling, practitioners can make operational adjustments to enhance remedy performance by considering potential biofouling controls in the design; balancing site-specific strategy and diagnostics; and proactively adjusting and fine tuning control/prevention technology and methodology.Ultimately, a combination of chemical and physical methods may be required to operate a carbon handling system over the long term; however, the operational costs can be greatly reduced and delivery efficiency increased if these methods are understood during the design phase. O