Wildlife deaths and deformities caused by selenium (Se) from drainage flows in the Kesterson National Wildlife Refuge provided the link between geology, irrigation return flows, and Se toxicity levels. Investigations found high levels of Se in the water, bottom sediment and biota throughout the Lower Gunnison and River Basin. Watershed-wide Se budgets indicate that about 61% of the Se delivered to Lake Powell via the Colorado River comes from drainage waters in the Gunnison River Basin and in the Grand Valley. The Gunnison Tunnel provides water to irrigate about 150,000 acres in the Uncompahgre and Grand Valleys. Impaired waters from irrigation seepage, return flows; drainage, and natural underground flows carry Se to the Upper Colorado River. Currently, commercial and residential development in the Lower Gunnison Basin is rapidly converting marginal lands to ranchettes, rural residential, and urban subdivisions. The availability of inexpensive water has the potential to mobilize Se. The Colorado State Non Point Source Management Protocol identified hydrologic impacts due to urbanization as a significant source of water quality impairment. Improper water management associated with new development on higher-Se soils has the potential to increase Se loading to the river. Water quality standards for the protection of wildlife vary between 2 µg/L and 4.6 g/L in the Colorado River system. There is increased regulatory pressure to apply a Total Maximum Daily Load (TMDL) requirement, which highlights the need to quantify and manage pollutant loadings from both agricultural and municipal sources.