Anthropogenic selenium contamination of aquatic ecosystems was first associated with cooling reservoirs of coal-fired power plants in the late 1970s, and later with drainage water from agricultural irrigation activities in the 1980s. In the 1990s, selenium contamination has been raised as a concern in the recovery of currently endangered fish in the Colorado River system. Widespread contamination from seleniferous drain waters from agriculture has been documented in the upper and lower Colorado River basins. Historically, irrigation started in the upper Colorado River basin in the late 1880s. In the 1930s, selenium concentrations in various drains, tributaries, and major rivers in the upper and lower Colorado River basins were in the 100 s and 1000 s of µg/L. Native fish inhabiting large rivers such as the Colorado pikeminnow and razorback sucker were abundant before 1890, but became rare after 1910 to 1920, before the influence of mainstem reservoirs in the upper and lower Colorado River. A hypothesis is presented that selenium contamination of the tributaries and major rivers of the Colorado River basin in the 1890 to 1910 period caused the decline of the endangered fish and continues to inhibit their recovery.