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Agriculture is a resource-intensive enterprise. The manner in which food production systems utilize resources has a large influence on environmental quality. To evaluate prospects for conserving natural resources while meeting increased demand for cereals, we interpret recent trends and future trajectories in crop yields, land and nitrogen fertilizer use, carbon sequestration, and greenhouse gas emissions to identify key issues and challenges. Based on this assessment, we conclude that avoiding expansion of cultivation into natural ecosystems, increased nitrogen use efficiency, and improved soil quality are pivotal components of a sustainable agriculture that meets human needs and protects natural resources. To achieve this outcome will depend on raising the yield potential and closing existing yield gaps of the major cereal crops to avoid yield stagnation in some of the world’s most productive systems. Recent trends suggest, however, that increasing crop yield potential is a formidable scientific challenge that has proven to be an elusive goal.