AbstractSince the initial use of Bordeaux mixture in 1885 for plant disease control, a large number of copper-based antimicrobial compounds (CBACs) have been developed and applied for crop protection. While these compounds have revolutionized crop protection in the twentieth century, their continuous and frequent use has also raised concerns about the long-term sustainability of copper (Cu)-based crop protection system. Here, we review CBACs used in crop protection and highlight their benefits and risks, and potential for their improvement and opportunities for further research to develop alternatives to CBACs. The major findings are (i) the relatively high toxicity to plant pathogens, low cost, low mammalian toxicity of the fixed Cu compounds, and their chemical stability and prolonged residual effects are major benefits of these compounds; (ii) phytotoxicity, development of copper-resistant strains, soil accumulation, and negative effects on soil biota as well as on food quality parameters are key disadvantages of CBACs; (iii) regulatory pressure in agriculture worldwide to limit the use of CBACs has led to several restrictions, including that imposed by the regulation 473/2002 in the European Union; and (iv) mitigation strategies to limit the negative effects of CBACs include their optimized use, soil remediation, and development and application of alternatives to CBACs for a sustainable crop protection. We conclude that recent research and policy efforts have led to the development of a number of alternatives to CBACs, which should be further intensified to ensure that growers have sufficient tools for the implementation of sustainable crop protection strategies.