Providing a fast growing world population with sufficient food while preserving ecological and energy resources of our planet is one of the biggest challenges in this century. Optimized management of chemical fertilizers and pesticides will be essential for achieving sustainability of intensive farming and requires both empirical data from field trials and advanced fundamental understanding of the molecular processes controlling plant growth. Genes involved in plant responses to nutrient deficiency and pathogen/herbivore attack have been identified, but we are lacking information about the cross-talk between signalling pathways when plants are exposed to a combination of abiotic and biotic stress factors. The focus of this review is on the relationship between the potassium status of plants and their susceptibility to pathogens and herbivorous insects. We combine field evidence on potassium–disease interaction with existing knowledge on metabolic and physiological factors that could explain such interaction, and present new data on metabolite profiles and hormonal pathways from the model plant Arabidopsis thaliana. The latter provides evidence that facilitated entry and development of pathogens or insects in(to) potassium-deficient plants as a result of physical and metabolic changes is counteracted by an increased defence. A genetic approach should now be applied to establish a causal relationship between disease susceptibility on the one hand and individual enzymatic and signal components on the other. Once identified, these can be used to design agricultural strategies that support the nutritional status of the crops while exploiting their inherent potential for defence.