In the US, waste byproducts generated from the treatment of municipal waste (biosolids and effluent), production of livestock (livestock waste), and drilling of oil and gas wells (drilling waste) are commonly applied to agricultural lands to fertilize soils. While land application of these wastes can be a cost-effective reuse/disposal practice, there is limited research on the potential for contaminant exposures and effects on ecosystems, wildlife, and human health that could result from land applications. In this presentation, we summarize results from extensive chemical, microbial, and toxicity analyses of biosolid, livestock, and drilling wastes prior to application on agricultural lands across the US. We also highlight on-going research by the USGS Ecosystem Mission Area that will aid the development of best-management practices. Our research can help maximize beneficial reuse of these wastes and minimize risk to the environment and human health to ensure a safer food supply and a healthier environment.