Copper-based nanomaterials (Cu-NMs) have been used increasingly in agriculture because they can increase crop productivity, pest control, and soil health. However, their toxicity and environmental safety have been a concern. Because of their small size and large surface area, Cu-NMs can dissolve with the release of Cu ions to disrupt biological processes. This can result in oxidative stress and plant health and productivity are dis-compromised. Additionally, Cu-NMs may inhibit nutrient uptake resulting in nutrient imbalances and lowered plant growth. Finally, Cu-NMs can have significant environmental impacts due to persistent occurrence in soil and water systems and the ability to impact soil microbiota and non-target organisms. There is a concern about human health risks, including heavy metal exposure from Cu-NMs that are bioaccumulating in food chains. Safe application practices, use of biodegradable or less toxic nanomaterial formulations and optimizing nanoparticle (NPs) concentrations are critical so that Cu-NMs can relieve toxicity in agricultural systems. An essential aspect of developing safer, more effective agricultural applications based on Cu-NM is that advanced nanomaterials with controlled release properties reduce the probability of Cu-NM accumulating in plants and soil. Finally, while they offer great promise for increasing agricultural productivity and crop protection, Cu-NMs can end up being toxic or pose unacceptable safety concerns. This chapter aims to provide overview on toxicity and safety concerns of copper-based nanomaterials in agriculture.