Secondary metabolites generally benefit their producers as poisons that protect them against competitors, predators or parasites. They are produced from universally present precursors (most often acetyl-CoA, amino acids or shikimate) by specific enzymes that probably arose by the duplication and divergence of genes originally coding for primary metabolism. Most secondary metabolites are restricted to single major taxa on the universal phylogenetic tree and so probably originated only once. But different secondary metabolic pathways have originated from different ancestral enzymes at radically different times in evolution. Secondary metabolites are most abundantly produced by microorganisms in crowded habitats and by plants, fungi and sessile animals like sponges, where chemical defence and attack rather than physical escape or fighting are at a premium. The first secondary metabolites were probably antibiotics produced in microbial mats over 3500 million years ago. These first ecosystems probably consisted entirely of eubacteria: archaebacteria and eukaryotes arose much later. As a phylogenetic context for considering the earliest origins of antibiotics I summarize a cladistic analysis of the explosive eubacterial primary diversification. This suggests that the most primitive surviving cells are the photosynthetic heliobacteria. Study of these and of the nearly as primitive chloroflexibacteria, spirochaetes and deinobacteria may provide the best evidence on the origins of secondary and primary metabolism.