<jats:p>MtrAB is a highly conserved two-component system implicated in the regulation of cell division in the Actinobacteria. It coordinates DNA replication with cell division in the unicellular <jats:italic>Mycobacterium tuberculosis</jats:italic> and links antibiotic production to sporulation in the filamentous <jats:italic>Streptomyces venezuelae.</jats:italic> Chloramphenicol biosynthesis is directly regulated by MtrA in <jats:italic>S. venezuelae</jats:italic> and deletion of <jats:italic>mtrB</jats:italic> constitutively activates MtrA and results in constitutive over-production of chloramphenicol. Here we report that in <jats:italic>Streptomyces coelicolor</jats:italic>, MtrA binds to sites upstream of developmental genes and the genes encoding ActII-1, ActII-4 and RedZ, which are cluster-situated regulators of the antibiotics actinorhodin (Act) and undecylprodigiosin (Red). Consistent with this, deletion of <jats:italic>mtrB</jats:italic> switches on the production of Act, Red and streptorubin B, a product of the Red pathway. Thus, we propose that MtrA is a key regulator that links antibiotic production to development and can be used to upregulate antibiotic production in distantly related streptomycetes.