Sewage sludge reuse will become crucial for the sustainability of agriculture, given the increasing population and the lack of essential nutrients for crop growth. Nevertheless, this practice raises some concerns, due to the large amounts of contaminants of emerging concern (CECs) present in sewage sludge, including pharmaceuticals and personal care products (PPCPs), microplastics (MPs), engineered nanomaterials (ENMs), per- and polyfluoroalkyl substances (PFASs), flame retardants, plasticizers, metals, antibiotic resistance bacteria (ARB) and resistance genes (ARGs). These CECs may adversely affect the environment and, ultimately, human health through the consumption of crops grown under sludge-amended soils. This chapter reviews the potential environmental and human health risks associated with sewage sludge reuse in agriculture, by focusing on relevant classes of CECs, such as PPCPs, MPs, carbon-based ENMs and considering ARBs and ARGs, a topic so far poorly addressed. The risks discussed focus on the contamination of aquatic and terrestrial ecosystems and on CECs uptake by crops intended for human consumption. Finally, technological strategies to improve sludge treatment, and thus minimize such risks, are briefly discussed.