The cyanobacterium Nostoc punctiforme can grow in a free-living state as multicellular vegetative filaments or as a plant symbiont. Symbiosis requires differentiation into infectious motile filaments termed hormogonia and can be stimulated by environmental conditions and by plant-derived hormogonium-inducing factors and is repressed by an unknown N. punctiforme hormogonium-repressing factor (HRF). Liaimer et al. analysed the effect of N. punctiforme secondary metabolites in the differentiation process and identified the nonribosomal peptide nostopeptolide as a HRF. Nostopeptolide was constitutively expressed in the free-living state and downregulated during plant symbiosis, and its addition was sufficient to repress hormogonia formation, demonstrating a role for this secondary metabolite during cell differentiation.