Koch’s postulates originally proposed a one microorganism–one disease approach to disease; however, it is now clear that many diseases of plants and animals are associated with changes in the taxonomic composition and function of the microbiome, and that health and disease are mediated by a dynamic interplay between host factors, environmental factors, the host microbiota and pathogenic microorganisms. Commensal microbes can become pathogenic under certain conditions, and disease can arise from complex polymicrobial infections. Although causation and correlation can be difficult to untangle, it is clear that the host microbiome plays a key role in resisting colonisation by pathogens across all host taxa, from plants to animals to humans. This offers exciting possibilities for manipulating microbiomes in order to reduce pathogenic infection in a range of contexts, including agriculture, wildlife and human health, through the use of probiotics, prebiotics and microbiome transplants, among other approaches.