Cereulide produced by Bacillus cereus sensu stricto and valinomycin synthesized mainly by Streptomyces spp. are natural dodecadepsipeptide ionophores that act as potassium transporters. Moreover, they comprise three repetitions of similar tetrapeptide motifs synthesized by nonribosomal peptide synthesis complexes. Resemblances in their structure find their reflections in the same way of action. The toxicity of valinomycin and cereulide is an effect of the disturbance of ionic equilibrium and transmembrane potential that may influence the whole organism and then cause fatal consequences. The vlm and ces operons encoding valinomycin and cereulide are both composed of two large, similar synthetase genes, one thioestrase gene and four other ORFs with unknown activities. In spite of the characterization of valinomycin and cereulide, genetic determinants encoding their biosynthesis have not yet been clarified.