Recycling and/or upcycling of agricultural byproducts containing valuable nutrients back into agricultural systems as bio-based fertilizers can improve the circularity and sustainability of food production. However, in some instances, there may be negative environmental consequences or safety concerns that need to be considered. This chapter discusses some common issues regarding the use of bio-based fertilizers, such as the concentration of nutrients leading to losses of reactive nitrogen and phosphorus into the environment. Potential issues with heavy metals, pathogens, antibiotics and other contaminants that can pose a health risk to humans, animals, crops and the ecosystem are also discussed. Finally, a case study investigating the effects of intensive livestock production on both reactive nitrogen losses and antibiotic resistance in the environment is presented. Recognizing and managing the risks associated with the use of bio-based fertilizers is necessary to fully integrate these products back into production systems, thereby enhancing the circularity of agriculture.