Plant pathology must contribute to improving food security in a safe operating space, which is shrinking as a result of declining natural resources, climate change, and the growing world population. This review analyzes the position of plant pathology in a nexus of relationships, which is mapped and where the coupled dynamics of crop growth, disease, and yield losses are modeled. We derive a hierarchy of pathogens, whereby pathogens reducing radiation interception (RI), radiation use efficiency (RUE), and harvest index increasingly impact crop yields in the approximate proportions: 1:4.5:4,700. Since the dawn of agriculture, plant breeding has targeted the harvest index as a main objective for domesticated plants. Surprisingly, the literature suggests that pathogens that reduce yields by directly damaging harvestable plant tissues have received much less attention than those that reduce RI or RUE. Ecological disease management needs to target diverse production situations and therefore must consider variation in attainable yields; this can be achieved through the reengineering of agrosystems to incorporate built-in dynamic diversity of genes, plants, and crop stands.