Concentrated animal feeding operations (CAFOs) generate large volumes of manure and manure-contaminated wash and runoff water. When applied to land at agronomic rates, CAFO wastewater has the potential to be a valuable fertilizer and soil amendment that can improve the physical condition of the soil for plant growth and reduce the demand for high quality water resources. However, excess amounts of nutrients, heavy metals, salts, pathogenic microorganisms, and pharmaceutically active compounds (antibiotics and hormones) in CAFO wastewater can adversely impact soil and water quality. The USEPA currently requires that application of CAFO wastes to agricultural lands follow an approved nutrient management plan (NMP). A NMP is a design document that sets rates for waste application to meet the water and nutrient requirements of the selected crops and soil types, and is typically written so as to be protective of surface water resources. The tacit assumption is that a well-designed and executed NMP ensures that all lagoon water contaminants are taken up or degraded in the root zone, so that ground water is inherently protected. The validity of this assumption for all lagoon water contaminants has not yet been thoroughly studied. This review paper discusses our current level of understanding on the environmental impact and sustainability of CAFO wastewater reuse. Specifically, we address the source, composition, application practices, environmental issues, transport pathways, and potential treatments that are associated with the reuse of CAFO wastewater on agricultural lands.