The quality of water distributed has become an increasingly serious issue as scientific evidence mounts about the negative impact on both wildlife and humans of pollutants released into the Greater Everglades due to human land use practices. Of all the challenges discussed, these may be the most difficult and costly to meet. The ecology of the Everglades evolved as a nutrient restricted system and can only thrive on very low concentrations of phosphorus and sulfates in its natural water supply.
- Nutrients such as phosphorus released from the agricultural areas near Lake Okeechobee can enter the Everglades National Park far to the south dramatically changing patterns of flora and fauna.
- Sulfur can also pollute the system since even seemingly moderate levels of sulfides are toxic to plants.
Native species such as sawgrass are three times more sensitive to sulfides than are their invasive competitors, cattails, which in some areas have changed the whole character of the ecosystem. 
- Even more disturbing, sulfates released by canals in the Everglades Agricultural Area can increase the production of Methyl Mercury (See Sulfur and Mercury), which enters the food chain, particularly fish, further to the south and can accumulate to dangerous levels to humans and wildlife, which eat fish.
Mercury contamination led the state of Florida to restrict consumption of nine species of fish in roughly 2 million acres of the Everglades. 
Of all the challenges discussed, these may be the most difficult and costly to meet.