The river drainages originating in the Cumberland region of Virginia, Tennessee and Kentucky are home to some of the last surviving and most diverse assemblages of native freshwater mussels. This region of the country also has historically and continues to be a major source of coal for the United States. Numerous experiments were carried out in an attempt to determine what ecotoxicological effects these activities have had on mussels as well as what has been done to correct some of the most severe cases of environmental pollution due to historical coal mining operations. Analysis of interstitial water (IW), sediment and in situ toxicity testing and chemical analyses showed that the most likely cause for mussel declines was elevated metal concentrations (Al, Cu, Fe, Pb) found in IW. Ecotoxicological assessments of the two streams (Black and Ely Creeks) most impacted by acid mine drainage (AMD) in the state of Virginia were carried out to determine their potential for future degradation of the Powell River watershed into which they drain. The Powell River is a major system still inhabited by native mussels. Sophisticated wetland systems built at Ely Creek have significantly improved the ecological health of Ely Creek, decreasing the pollution into the Powell River. Reclamation and wetland construction at Black Creek have had a positive impact but active coal mining and un-remediated AMD are still negatively affecting this system. After the watershed has been fully reclaimed the discharge from Black Creek will likely be improved.