Streptomyces species are (along with the fungi) the best-known antibiotic-producing organisms. Often, they make several different antibiotics. The biosynthesis of each antibiotic is encoded by a complex gene cluster that usually also contains regulatory and resistance genes. Typically, there may be more than one such pathway-specific regulatory gene per cluster. Both activator and repressor genes are known. Some of the regulatory genes for different pathways are related. In S. coelicolor, expression of several such biosynthetic gene clusters also depends on at least 11 globally acting genes, at least one of which is involved in the translation of a rare codon (UUA). A protein phosphorylation cascade also seems to be involved. Gene clusters closely similar to those for the biosynthesis of aromatic polyketide antibiotics determine spore pigment in some species. These genes show different regulation from antibiotic production genes. The evolution of gene clusters for polyketide antibiotics, and the possible adaptive benefits of secondary metabolism, are discussed.